Scholars@Duke
James O'Connell McNamara Sr.

James O'Connell McNamara Sr.

Duke School of Medicine Distinguished Professor in Neuroscience
Neurobiology
jmc@neuro.duke.edu
BOX3209, Durham, NC 27710
Bryan Research Building, 311 Research Driveroom 401C, Durham, NC 27710
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Selected Publications

A fluorogenic micrococcal nuclease-based probe for fast detection and optical imaging of Staphylococcus aureus in prosthetic joint and fracture-related infections.

Journal Article Eur J Nucl Med Mol Imaging · August 2024 PURPOSE: Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapi ... Full text Link to item Cite

A simple, automated method of seizure detection in mouse models of temporal lobe epilepsy.

Journal Article Epilepsy Res · December 2023 The lack of preventive and disease modifying therapies for temporal lobe epilepsy (TLE) is a major unmet medical need. Search for such therapies utilize mouse models and require detection of seizures in electroencephalography (EEG) recordings. The labor-in ... Full text Link to item Cite

A team science approach for the preclinical and clinical characterization and biomarker development for post-traumatic epilepsy

Journal Article Epilepsia Open · September 1, 2023 Objective: Post-traumatic epilepsy (PTE) is an acquired epilepsy that develops in the months or years following a traumatic brain injury (TBI) and can lead to substantial personal, financial, and societal burden. To date, PTE is rarely curable; current tre ... Full text Cite

Long-Term Potentiation of Mossy Fiber Feedforward Inhibition of CA3 Pyramidal Cells Maintains E/I Balance in Epilepsy Model.

Journal Article eNeuro · 2022 Insight into the cellular and circuit mechanisms underlying development of temporal lobe epilepsy (TLE) will provide a foundation for improved therapies. We studied a model in which an episode of prolonged seizures is followed by recovery lasting two weeks ... Full text Link to item Cite

Intravenous kainic acid induces status epilepticus and late onset seizures in mice.

Journal Article Epilepsy Res · December 2021 We set out to establish a novel model of temporal lobe epilepsy (TLE) in a mouse. We sought to induce TLE through the injection of kainic acid (KA) into the tail vein with subsequent development of status epilepticus (SE). Using C57BL/6 mice, we implanted ... Full text Link to item Cite

Cnksr2 Loss in Mice Leads to Increased Neural Activity and Behavioral Phenotypes of Epilepsy-Aphasia Syndrome.

Journal Article J Neurosci · November 17, 2021 Epilepsy Aphasia Syndromes (EAS) are a spectrum of childhood epileptic, cognitive, and language disorders of unknown etiology. CNKSR2 is a strong X-linked candidate gene implicated in EAS; however, there have been no studies of genetic models to dissect ho ... Full text Link to item Cite

Antiepileptogenesis and disease modification: Clinical and regulatory issues.

Journal Article Epilepsia Open · September 2021 This is a summary report of clinical and regulatory issues discussed at the 2018 NINDS workshop, entitled "Accelerating Therapies for Antiepileptogenesis and Disease Modification." The intent of the workshop was to optimize and accelerate development of th ... Full text Link to item Cite

The smart activatable P2&3TT probe allows accurate, fast, and highly sensitive detection of Staphylococcus aureus in clinical blood culture samples.

Journal Article Sci Rep · November 5, 2020 Staphylococcus aureus bacteraemia (SAB) is associated with high mortality and morbidity rates. Yet, there is currently no adequate diagnostic test for early and rapid diagnosis of SAB. Therefore, this study was aimed at exploring the potential for clinical ... Full text Link to item Cite

Targeting BDNF/TrkB pathways for preventing or suppressing epilepsy.

Journal Article Neuropharmacology · May 1, 2020 Traumatic brain injury (TBI) and status epilepticus (SE) have both been linked to development of human epilepsy. Although distinct etiologies, current research has suggested the convergence of molecular mechanisms underlying epileptogenesis following these ... Full text Link to item Cite

Regression of Epileptogenesis by Inhibiting Tropomyosin Kinase B Signaling following a Seizure.

Journal Article Ann Neurol · December 2019 OBJECTIVE: Temporal lobe epilepsy (TLE) is a devastating disease in which seizures persist in 35% of patients despite optimal use of antiseizure drugs. Clinical and preclinical evidence implicates seizures themselves as one factor promoting epilepsy progre ... Full text Open Access Link to item Cite

Small Animal Multivariate Brain Analysis (SAMBA) - a High Throughput Pipeline with a Validation Framework.

Journal Article Neuroinformatics · July 2019 While many neuroscience questions aim to understand the human brain, much current knowledge has been gained using animal models, which replicate genetic, structural, and connectivity aspects of the human brain. While voxel-based analysis (VBA) of preclinic ... Full text Link to item Cite

TrkB-Shc Signaling Protects against Hippocampal Injury Following Status Epilepticus.

Journal Article J Neurosci · June 5, 2019 Temporal lobe epilepsy (TLE) is a common and commonly devastating form of human epilepsy for which only symptomatic therapy is available. One cause of TLE is an episode of de novo prolonged seizures [status epilepticus (SE)]. Understanding the molecular si ... Full text Open Access Link to item Cite

LTD at mossy fiber synapses onto stratum lucidum interneurons requires TrkB and retrograde endocannabinoid signaling.

Journal Article J Neurophysiol · February 1, 2019 Hippocampal mossy fiber axons simultaneously activate CA3 pyramidal cells and stratum lucidum interneurons (SLINs), the latter providing feedforward inhibition to control CA3 pyramidal cell excitability. Filopodial extensions of giant boutons of mossy fibe ... Full text Link to item Cite

Transcriptional profile of hippocampal dentate granule cells in four rat epilepsy models.

Journal Article Sci Data · May 9, 2017 Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression cha ... Full text Open Access Link to item Cite

Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex.

Journal Article J Neurochem · February 2017 Vagal Nerve Stimulation (VNS) Therapy® is a United States Food and Drug Administration approved neurotherapeutic for medically refractory partial epilepsy and treatment-resistant depression. The molecular mechanisms underlying its beneficial effects are un ... Full text Link to item Cite

Is FGF13 a major contributor to genetic epilepsy with febrile seizures plus?

Journal Article Epilepsy Res · December 2016 Mutation of fibroblast growth factor 13 (FGF13) has recently been implicated in genetic epilepsy with febrile seizures plus (GEFS+) in a single family segregating a balanced translocation with a breakpoint in this X chromosome gene, predicting a partial kn ... Full text Link to item Cite

Autocrine BDNF-TrkB signalling within a single dendritic spine.

Journal Article Nature · October 6, 2016 Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are crucial for many forms of neuronal plasticity, including structural long-term potentiation (sLTP), which is a correlate of an animal's learning. However, it is unknown whether BDNF release ... Full text Link to item Cite

A fluorogenic micrococcal nuclease-based probe for fast detection and optical imaging of Staphylococcus aureus in prosthetic joint and fracture-related infections.

Journal Article Eur J Nucl Med Mol Imaging · August 2024 PURPOSE: Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapi ... Full text Link to item Cite

A simple, automated method of seizure detection in mouse models of temporal lobe epilepsy.

Journal Article Epilepsy Res · December 2023 The lack of preventive and disease modifying therapies for temporal lobe epilepsy (TLE) is a major unmet medical need. Search for such therapies utilize mouse models and require detection of seizures in electroencephalography (EEG) recordings. The labor-in ... Full text Link to item Cite

A team science approach for the preclinical and clinical characterization and biomarker development for post-traumatic epilepsy

Journal Article Epilepsia Open · September 1, 2023 Objective: Post-traumatic epilepsy (PTE) is an acquired epilepsy that develops in the months or years following a traumatic brain injury (TBI) and can lead to substantial personal, financial, and societal burden. To date, PTE is rarely curable; current tre ... Full text Cite

Long-Term Potentiation of Mossy Fiber Feedforward Inhibition of CA3 Pyramidal Cells Maintains E/I Balance in Epilepsy Model.

Journal Article eNeuro · 2022 Insight into the cellular and circuit mechanisms underlying development of temporal lobe epilepsy (TLE) will provide a foundation for improved therapies. We studied a model in which an episode of prolonged seizures is followed by recovery lasting two weeks ... Full text Link to item Cite

Intravenous kainic acid induces status epilepticus and late onset seizures in mice.

Journal Article Epilepsy Res · December 2021 We set out to establish a novel model of temporal lobe epilepsy (TLE) in a mouse. We sought to induce TLE through the injection of kainic acid (KA) into the tail vein with subsequent development of status epilepticus (SE). Using C57BL/6 mice, we implanted ... Full text Link to item Cite

Cnksr2 Loss in Mice Leads to Increased Neural Activity and Behavioral Phenotypes of Epilepsy-Aphasia Syndrome.

Journal Article J Neurosci · November 17, 2021 Epilepsy Aphasia Syndromes (EAS) are a spectrum of childhood epileptic, cognitive, and language disorders of unknown etiology. CNKSR2 is a strong X-linked candidate gene implicated in EAS; however, there have been no studies of genetic models to dissect ho ... Full text Link to item Cite

Antiepileptogenesis and disease modification: Clinical and regulatory issues.

Journal Article Epilepsia Open · September 2021 This is a summary report of clinical and regulatory issues discussed at the 2018 NINDS workshop, entitled "Accelerating Therapies for Antiepileptogenesis and Disease Modification." The intent of the workshop was to optimize and accelerate development of th ... Full text Link to item Cite

The smart activatable P2&3TT probe allows accurate, fast, and highly sensitive detection of Staphylococcus aureus in clinical blood culture samples.

Journal Article Sci Rep · November 5, 2020 Staphylococcus aureus bacteraemia (SAB) is associated with high mortality and morbidity rates. Yet, there is currently no adequate diagnostic test for early and rapid diagnosis of SAB. Therefore, this study was aimed at exploring the potential for clinical ... Full text Link to item Cite

Targeting BDNF/TrkB pathways for preventing or suppressing epilepsy.

Journal Article Neuropharmacology · May 1, 2020 Traumatic brain injury (TBI) and status epilepticus (SE) have both been linked to development of human epilepsy. Although distinct etiologies, current research has suggested the convergence of molecular mechanisms underlying epileptogenesis following these ... Full text Link to item Cite

Regression of Epileptogenesis by Inhibiting Tropomyosin Kinase B Signaling following a Seizure.

Journal Article Ann Neurol · December 2019 OBJECTIVE: Temporal lobe epilepsy (TLE) is a devastating disease in which seizures persist in 35% of patients despite optimal use of antiseizure drugs. Clinical and preclinical evidence implicates seizures themselves as one factor promoting epilepsy progre ... Full text Open Access Link to item Cite

Small Animal Multivariate Brain Analysis (SAMBA) - a High Throughput Pipeline with a Validation Framework.

Journal Article Neuroinformatics · July 2019 While many neuroscience questions aim to understand the human brain, much current knowledge has been gained using animal models, which replicate genetic, structural, and connectivity aspects of the human brain. While voxel-based analysis (VBA) of preclinic ... Full text Link to item Cite

TrkB-Shc Signaling Protects against Hippocampal Injury Following Status Epilepticus.

Journal Article J Neurosci · June 5, 2019 Temporal lobe epilepsy (TLE) is a common and commonly devastating form of human epilepsy for which only symptomatic therapy is available. One cause of TLE is an episode of de novo prolonged seizures [status epilepticus (SE)]. Understanding the molecular si ... Full text Open Access Link to item Cite

LTD at mossy fiber synapses onto stratum lucidum interneurons requires TrkB and retrograde endocannabinoid signaling.

Journal Article J Neurophysiol · February 1, 2019 Hippocampal mossy fiber axons simultaneously activate CA3 pyramidal cells and stratum lucidum interneurons (SLINs), the latter providing feedforward inhibition to control CA3 pyramidal cell excitability. Filopodial extensions of giant boutons of mossy fibe ... Full text Link to item Cite

Transcriptional profile of hippocampal dentate granule cells in four rat epilepsy models.

Journal Article Sci Data · May 9, 2017 Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression cha ... Full text Open Access Link to item Cite

Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex.

Journal Article J Neurochem · February 2017 Vagal Nerve Stimulation (VNS) Therapy® is a United States Food and Drug Administration approved neurotherapeutic for medically refractory partial epilepsy and treatment-resistant depression. The molecular mechanisms underlying its beneficial effects are un ... Full text Link to item Cite

Is FGF13 a major contributor to genetic epilepsy with febrile seizures plus?

Journal Article Epilepsy Res · December 2016 Mutation of fibroblast growth factor 13 (FGF13) has recently been implicated in genetic epilepsy with febrile seizures plus (GEFS+) in a single family segregating a balanced translocation with a breakpoint in this X chromosome gene, predicting a partial kn ... Full text Link to item Cite

Autocrine BDNF-TrkB signalling within a single dendritic spine.

Journal Article Nature · October 6, 2016 Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are crucial for many forms of neuronal plasticity, including structural long-term potentiation (sLTP), which is a correlate of an animal's learning. However, it is unknown whether BDNF release ... Full text Link to item Cite

Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity.

Journal Article Nature · October 6, 2016 The Rho GTPase proteins Rac1, RhoA and Cdc42 have a central role in regulating the actin cytoskeleton in dendritic spines, thereby exerting control over the structural and functional plasticity of spines and, ultimately, learning and memory. Although previ ... Full text Link to item Cite

A Peptide Uncoupling BDNF Receptor TrkB from Phospholipase Cγ1 Prevents Epilepsy Induced by Status Epilepticus.

Journal Article Neuron · November 4, 2015 The BDNF receptor tyrosine kinase, TrkB, underlies nervous system function in both health and disease. Excessive activation of TrkB caused by status epilepticus promotes development of temporal lobe epilepsy (TLE), revealing TrkB as a therapeutic target fo ... Full text Open Access Link to item Cite

Disruption of Fgf13 causes synaptic excitatory-inhibitory imbalance and genetic epilepsy and febrile seizures plus.

Journal Article J Neurosci · June 10, 2015 We identified a family in which a translocation between chromosomes X and 14 was associated with cognitive impairment and a complex genetic disorder termed "Genetic Epilepsy and Febrile Seizures Plus" (GEFS(+)). We demonstrate that the breakpoint on the X ... Full text Link to item Cite

Brain-derived neurotrophic factor but not vesicular zinc promotes TrkB activation within mossy fibers of mouse hippocampus in vivo.

Journal Article J Comp Neurol · December 1, 2014 The neurotrophin receptor, TrkB receptor tyrosine kinase, is critical to central nervous system (CNS) function in health and disease. Elucidating the ligands mediating TrkB activation in vivo will provide insights into its diverse roles in the CNS. The can ... Full text Link to item Cite

Antiseizure effects of TrkB kinase inhibition.

Journal Article Epilepsia · August 2014 OBJECTIVE: The principal molecular targets of conventional antiseizure drugs consist of ligand-gated and voltage-gated ion channels and proteins subserving synaptic function. Inhibition of the receptor tyrosine kinase TrkB limits epileptogenesis, but its e ... Full text Link to item Cite

Impairment of kindling development in phospholipase Cγ1 heterozygous mice.

Journal Article Epilepsia · March 2014 OBJECTIVE: Elucidating molecular mechanisms underlying limbic epileptogenesis may reveal novel targets for preventive therapy. Studies of TrkB mutant mice led us to hypothesize that signaling through a specific phospholipase (PLC), PLCγ1, promoted developm ... Full text Link to item Cite

Aligning animal models with clinical epilepsy: where to begin?

Journal Article Adv Exp Med Biol · 2014 Treatment of the epilepsies have benefitted immensely from study of animal models, most notably in the development of diverse anti-seizure medications in current clinical use. However, available drugs provide only symptomatic relief from seizures and are o ... Full text Link to item Cite

Aligning animal models with clinical epilepsy: Where to begin?

Journal Article Advances in Experimental Medicine and Biology · January 1, 2014 Treatment of the epilepsies have benefitted immensely from study of animal models, most notably in the development of diverse anti-seizure medications in current clinical use. However, available drugs provide only symptomatic relief from seizures and are o ... Full text Cite

Aligning animal models with clinical epilepsy: Where to begin?

Journal Article Advances in Experimental Medicine and Biology · January 1, 2014 Treatment of the epilepsies have benefitted immensely from study of animal models, most notably in the development of diverse anti-seizure medications in current clinical use. However, available drugs provide only symptomatic relief from seizures and are o ... Full text Cite

Morphological changes among hippocampal dentate granule cells exposed to early kindling-epileptogenesis.

Journal Article Hippocampus · December 2013 Temporal lobe epilepsy is associated with changes in the morphology of hippocampal dentate granule cells. These changes are evident in numerous models that are associated with substantial neuron loss and spontaneous recurrent seizures. By contrast, previou ... Full text Link to item Cite

Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.

Journal Article Neuron · October 16, 2013 We analyzed four families that presented with a similar condition characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. We show that recessive mutations in the ASNS gene are responsible f ... Full text Link to item Cite

Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy.

Journal Article Neuron · July 10, 2013 Temporal lobe epilepsy is the most common and often devastating form of human epilepsy. The molecular mechanism underlying the development of temporal lobe epilepsy remains largely unknown. Emerging evidence suggests that activation of the BDNF receptor Tr ... Full text Open Access Link to item Cite

In search of the ever-elusive positive endozepine.

Journal Article Neuron · June 19, 2013 In this issue of Neuron, Christian et al. (2013) provide functional evidence for positive endozepines (positive allosteric modulators of GABAARs) within the thalamic reticular nucleus. These molecules are encoded by the Dbi gene and modulate thalamocortica ... Full text Link to item Cite

The auxiliary subunit KChIP2 is an essential regulator of homeostatic excitability.

Journal Article J Biol Chem · May 10, 2013 BACKGROUND: The necessity for, or redundancy of, distinctive KChIP proteins is not known. RESULTS: Deletion of KChIP2 leads to increased susceptibility to epilepsy and to a reduction in IA and increased excitability in pyramidal hippocampal neurons. CONCLU ... Full text Link to item Cite

The cellular and synaptic location of activated TrkB in mouse hippocampus during limbic epileptogenesis.

Journal Article J Comp Neurol · February 15, 2013 Understanding the mechanisms of limbic epileptogenesis in cellular and molecular terms may provide novel therapeutic targets for its prevention. The neurotrophin receptor tropomyosin-related kinase B (TrkB) is thought to be critical for limbic epileptogene ... Full text Link to item Cite

Reply: To PMID 22653543.

Journal Article Retina · 2013 Full text Link to item Cite

The Epilepsies: Phenotypes and Mechanisms

Journal Article · December 1, 2012 Full text Cite

Conditional deletion of TrkC does not modify limbic epileptogenesis.

Journal Article Epilepsy Res · November 2012 The neurotrophin receptor, tropomyosin-related kinase B (TrkB), is required for epileptogenesis in the kindling model. The role of a closely related neurotrophin receptor, TrkC, in limbic epileptogenesis is unknown. We examined limbic epileptogenesis in th ... Full text Link to item Cite

Vagus nerve stimulation elevates seizure threshold in the kindling model.

Journal Article Epilepsia · November 2012 PURPOSE:   Vagus nerve stimulation (VNS) provides partial relief of medically refractory partial seizures in a subset of patients. The optimal pattern of stimulation and the mechanism of the antiseizure effects are uncertain. Establishing the efficacy of V ... Full text Link to item Cite

Neuroprotective effects of reactive oxygen species mediated by BDNF-independent activation of TrkB.

Journal Article J Neurosci · October 31, 2012 Reactive oxygen species (ROS) have diverse biological consequences in the mammalian CNS, but the molecular targets mediating these pleiotropic effects are incompletely understood. Like ROS, the neurotrophin receptor, TrkB receptor tyrosine kinase, has dive ... Full text Link to item Cite

Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy.

Journal Article Am J Hum Genet · August 10, 2012 Idiopathic generalized epilepsy (IGE) is a complex disease with high heritability, but little is known about its genetic architecture. Rare copy-number variants have been found to explain nearly 3% of individuals with IGE; however, it remains unclear wheth ... Full text Link to item Cite

Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA aptamers.

Journal Article Nucleic Acids Res · July 2012 Human epidermal growth factor receptor 2 (HER2) expression in breast cancer is associated with an aggressive phenotype and poor prognosis, making it an appealing therapeutic target. Trastuzumab, an HER2 antibody-based inhibitor, is currently the leading ta ... Full text Link to item Cite

Degradation of nuclease-stabilized RNA oligonucleotides in Mycoplasma-contaminated cell culture media.

Journal Article Nucleic Acid Ther · February 2012 Artificial RNA reagents such as small interfering RNAs (siRNAs) and aptamers often must be chemically modified for optimal effectiveness in environments that include ribonucleases. Mycoplasmas are common bacterial contaminants of mammalian cell cultures th ... Full text Link to item Cite

Vesicular zinc promotes presynaptic and inhibits postsynaptic long-term potentiation of mossy fiber-CA3 synapse.

Journal Article Neuron · September 22, 2011 The presence of zinc in glutamatergic synaptic vesicles of excitatory neurons of mammalian cerebral cortex suggests that zinc might regulate plasticity of synapses formed by these neurons. Long-term potentiation (LTP) is a form of synaptic plasticity that ... Full text Link to item Cite

Temporal lobe epilepsy and the BDNF receptor, TrkB

Journal Article Epilepsia · December 1, 2010 Brain derived neurotrophic factor (BDNF) regulates diverse neuronal functions and plasticity, and its expression is increased by seizures. Here we review the evidence that actions of BDNF at TrkB receptors contribute to temporal lobe epilepsy. In addition, ... Full text Cite

Porous biocompatible three-dimensional scaffolds of cellulose microfiber/gelatin composites for cell culture.

Journal Article Acta Biomater · June 2010 Physiological tissues, including brain and other organs, have three-dimensional (3-D) aspects that need to be supported to model them in vitro. Here we report the use of cellulose microfibers combined with cross-linked gelatin to make biocompatible porous ... Full text Link to item Cite

TrkB signaling is required for behavioral sensitization and conditioned place preference induced by a single injection of cocaine.

Journal Article Neuropharmacology · June 2010 Exogenous brain-derived neurotrophic factor (BDNF) can regulate behavioral sensitization and conditioned place preference (CPP) when animals are exposed to repeated cocaine administration. However, it is unclear whether BDNF signaling through the TrkB rece ... Full text Link to item Cite

Reduction of TrkB expression de novo in the adult mouse impairs epileptogenesis in the kindling model.

Journal Article Hippocampus · June 2010 Elucidating the mechanisms of epileptogenesis in molecular terms can identify targets for therapies aimed at preventing epileptogenesis or limiting its progression. Genetic perturbations have implicated signaling by the neurotrophin, BDNF, and its receptor ... Full text Link to item Cite

Disruption of TrkB-mediated phospholipase Cgamma signaling inhibits limbic epileptogenesis.

Journal Article J Neurosci · May 5, 2010 The BDNF receptor, TrkB, is critical to limbic epileptogenesis, but the responsible downstream signaling pathways are unknown. We hypothesized that TrkB-dependent activation of phospholipase Cgamma1 (PLCgamma1) signaling is the key pathway and tested this ... Full text Link to item Cite

Mutual regulation of Src family kinases and the neurotrophin receptor TrkB.

Journal Article J Biol Chem · March 12, 2010 The neurotrophin receptor tyrosine kinase TrkB is critical to diverse biological processes. We investigated the interplay of Src family kinases (SFKs) and TrkB to better understand mechanisms of TrkB signaling in physiological and pathological conditions. ... Full text Link to item Cite

Structural plasticity of dentate granule cell mossy fibers during the development of limbic epilepsy.

Journal Article Hippocampus · January 2010 Altered granule cell>>CA3 pyramidal cell synaptic connectivity may contribute to the development of limbic epilepsy. To explore this possibility, granule cell giant mossy fiber bouton plasticity was examined in the kindling and pilocarpine models of epilep ... Full text Link to item Cite

Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors.

Journal Article Nat Biotechnol · September 2009 Prostate cancer cells expressing prostate-specific membrane antigen (PSMA) have been targeted with RNA aptamer-small interfering (si)RNA chimeras, but therapeutic efficacy in vivo was demonstrated only with intratumoral injection. Clinical translation of t ... Full text Link to item Cite

Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors.

Journal Article Neuron · July 16, 2009 Examining the behavioral consequences of selective CNS neuronal activation is a powerful tool for elucidating mammalian brain function in health and disease. Newly developed genetic, pharmacological, and optical tools allow activation of neurons with exqui ... Full text Link to item Cite

Synthesis of magnetic porous hollow silica nanotubes for drug delivery

Journal Article Journal of Applied Physics · April 27, 2009 In this paper, we report a synthesis of magnetic porous hollow silica nanotubes (MPHSNTs) using sol-gel method. The MPHSNTs were fabricated by coating Fe3 O4 nanoparticles and silica on surfactant hexadecyltrimethylammonium bromide (CTAB) modified CaCO3 na ... Full text Cite

Cell-specific aptamers for targeted therapies.

Journal Article Methods Mol Biol · 2009 Many signalling proteins involved in diverse functions such as cell growth and differentiation can act as oncogenes and cause cellular transformation. These molecules represent attractive targets for cancer diagnosis or therapy and therefore are subject to ... Full text Link to item Cite

Plasticity of dentate granule cell mossy fiber synapses: A Putative mechanism of limbic epileptogenesis

Journal Article · December 1, 2008 The epilepsies constitute the third most common serious neurological disorder. Among the more than 40 different types of epilepsy, limbic epilepsy is the single most common and devastating form. Antiseizure drugs provide symptomatic relief, in that they su ... Full text Cite

Enantiomeric propanolamines as selective N-methyl-D-aspartate 2B receptor antagonists.

Journal Article J Med Chem · September 25, 2008 Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and sel ... Full text Link to item Cite

In vivo profile of ICA-27243 [N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide], a potent and selective KCNQ2/Q3 (Kv7.2/Kv7.3) activator in rodent anticonvulsant models.

Journal Article J Pharmacol Exp Ther · September 2008 Openers or activators of neuronal KCNQ2/Q3 potassium channels decrease neuronal excitability and may provide benefit in the treatment of disorders of neuronal excitability such as epilepsy. In the present study, we evaluate the effects of ICA-27243 [N-(6-c ... Full text Link to item Cite

Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse.

Journal Article Neuron · February 28, 2008 The receptor tyrosine kinase, TrkB, is critical to diverse functions of the mammalian nervous system in health and disease. Evidence of TrkB activation during epileptogenesis in vivo despite genetic deletion of its prototypic neurotrophin ligands led us to ... Full text Link to item Cite

Altered morphology of hippocampal dentate granule cell presynaptic and postsynaptic terminals following conditional deletion of TrkB.

Journal Article Hippocampus · 2008 Dentate granule cells play a critical role in the function of the entorhinal-hippocampal circuitry in health and disease. Dentate granule cells are situated to regulate the flow of information into the hippocampus, a structure required for normal learning ... Full text Link to item Cite

Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice.

Journal Article J Clin Invest · January 2008 4-1BB is a major costimulatory receptor that promotes the survival and expansion of activated T cells. Administration of agonistic anti-4-1BB Abs has been previously shown to enhance tumor immunity in mice. Abs are cell-based products posing significant co ... Full text Link to item Cite

Multicentre search for genetic susceptibility loci in sporadic epilepsy syndrome and seizure types: a case-control study.

Journal Article Lancet Neurol · November 2007 BACKGROUND: The Epilepsy Genetics (EPIGEN) Consortium was established to undertake genetic mapping analyses with augmented statistical power to detect variants that influence the development and treatment of common forms of epilepsy. METHODS: We examined c ... Full text Link to item Cite

Does epileptiform activity contribute to cognitive impairment in Alzheimer's disease?

Journal Article Neuron · September 6, 2007 Alzheimer's disease is a devastating neurological disorder. The role of hyperexcitability in the disease's cognitive decline is not completely understood. In this issue of Neuron, Palop et al. report both limbic seizures and presumed homeostatic responses ... Full text Link to item Cite

An Animal Model of Rasmussen's Encephalitis

Journal Article · December 1, 2006 Full text Cite

Molecular signaling mechanisms underlying epileptogenesis.

Journal Article Sci STKE · October 10, 2006 Featured Publication Epilepsy, a disorder of recurrent seizures, is a common and frequently devastating neurological condition. Available therapy is only symptomatic and often ineffective. Understanding epileptogenesis, the process by which a normal brain becomes epileptic, ma ... Full text Link to item Cite

Impaired volume regulation is the mechanism of excitotoxic sensitization to complement.

Journal Article J Neurosci · October 4, 2006 Previous work demonstrated that a brief, sublethal excitotoxic insult strikingly increased the sensitivity of cortical neurons to the cytotoxic effects of the terminal pathway of complement, a process termed "excitotoxic sensitization." Here, we sought to ... Full text Link to item Cite

Plasticity of both excitatory and inhibitory synapses is associated with seizures induced by removal of chronic blockade of activity in cultured hippocampus.

Journal Article J Neurophysiol · October 2006 One factor common to many neurological insults that can lead to acquired epilepsy is a loss of afferent neuronal input. Neuronal activity is one cellular mechanism implicated in transducing deafferentation into epileptogenesis. Therefore the effects of chr ... Full text Link to item Cite

The tyrosine receptor kinase B ligand, neurotrophin-4, is not required for either epileptogenesis or tyrosine receptor kinase B activation in the kindling model.

Journal Article Neuroscience · August 11, 2006 The kindling model of epilepsy is a form of neuronal plasticity induced by repeated induction of pathological activity in the form of focal seizures. A causal role for the neurotrophin receptor, tyrosine receptor kinase B, in epileptogenesis is supported b ... Full text Link to item Cite

Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras.

Journal Article Nat Biotechnol · August 2006 Technologies that mediate targeted delivery of small interfering RNAs (siRNAs) are needed to improve their therapeutic efficacy and safety. Therefore, we have developed aptamer-siRNA chimeric RNAs capable of cell type-specific binding and delivery of funct ... Full text Link to item Cite

VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms.

Journal Article Neuropsychopharmacology · July 2006 Currently available therapeutic interventions for treatment-resistant depression, including switch, combination, and augmentation strategies, are less than ideal. Observations of mood elevation during vagus nerve stimulation (VNS) therapy for pharmacoresis ... Full text Link to item Cite

Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival.

Journal Article Biochem Biophys Res Commun · December 16, 2005 Alphavbeta3 integrin is a crucial factor involved in a variety of physiological processes, such as cell growth and migration, tumor invasion and metastasis, angiogenesis, and wound healing. Alphavbeta3 integrin exerts its effect by regulating endothelial c ... Full text Link to item Cite

A locus for generalized tonic-clonic seizure susceptibility maps to chromosome 10q25-q26.

Journal Article Ann Neurol · September 2005 Inheritance patterns in twins and multiplex families led us to hypothesize that two loci were segregating in subjects with juvenile myoclonic epilepsy (JME), one predisposing to generalized tonic-clonic seizures (GTCS) and a second to myoclonic seizures. W ... Full text Link to item Cite

Translation of an integral membrane protein in distal dendrites of hippocampal neurons.

Journal Article Eur J Neurosci · March 2005 Maintenance of synaptic plasticity requires protein translation. Because changes in synaptic strength are regulated at the level of individual synapses, a mechanism is required for newly translated proteins to specifically and persistently modify only a su ... Full text Link to item Cite

Localization of brain-derived neurotrophic factor to distinct terminals of mossy fiber axons implies regulation of both excitation and feedforward inhibition of CA3 pyramidal cells.

Journal Article J Neurosci · December 15, 2004 Hippocampal dentate granule cells directly excite and indirectly inhibit CA3 pyramidal cells via distinct presynaptic terminal specializations of their mossy fiber axons. This mossy fiber pathway contains the highest concentration of brain-derived neurotro ... Full text Link to item Cite

Contributions of mossy fiber and CA1 pyramidal cell sprouting to dentate granule cell hyperexcitability in kainic acid-treated hippocampal slice cultures.

Journal Article J Neurophysiol · December 2004 Axonal sprouting like that of the mossy fibers is commonly associated with temporal lobe epilepsy, but its significance remains uncertain. To investigate the functional consequences of sprouting of mossy fibers and alternative pathways, kainic acid (KA) wa ... Full text Link to item Cite

Ischemic stroke: "acidotoxicity" is a perpetrator.

Journal Article Cell · September 17, 2004 Ischemic stroke is a devastating neurological disease. The responsible mechanisms are not completely understood. In this issue of Cell, Xiong et al. (2004) elucidate a molecular mechanism by which acidosis damages the brain during ischemia. ... Full text Link to item Cite

A galactosylceramide binding domain is involved in trafficking of CLN3 from Golgi to rafts via recycling endosomes.

Journal Article Pediatr Res · September 2004 Juvenile neuronal ceroid lipofuscinosis (JNCL) is due to mutations in the CLN3 gene. We previously determined that CLN3 protein harbors a highly conserved motif, VYFAE, necessary for its impact on cell growth and apoptosis. Using molecular modeling we demo ... Full text Link to item Cite

Rapid dendritic transport of TGN38, a putative cargo receptor.

Journal Article Brain Res Mol Brain Res · August 23, 2004 Protein transport to and from the postsynaptic plasma membrane is thought to be of central importance for synaptic plasticity. However, the molecular details of such processes are poorly understood. One mechanism by which membrane and secretory proteins ma ... Full text Link to item Cite

Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model.

Journal Article Neuron · July 8, 2004 Featured Publication Epileptogenesis is the process whereby a normal brain becomes epileptic. We hypothesized that the neurotrophin brain-derived neurotrophic factor (BDNF) activates its receptor, TrkB, in the hippocampus during epileptogenesis and that BDNF-mediated activatio ... Full text Link to item Cite

Ontogeny of seizure-induced increases in BDNF immunoreactivity and TrkB receptor activation in rat hippocampus.

Journal Article Hippocampus · 2004 The present work tested the hypothesis that the anatomic and developmental patterns of status epilepticus-induced increases of brain-derived neurotrophic factor (BDNF) protein coincided with status epilepticus-induced increases of phospho-Trk immunoreactiv ... Full text Link to item Cite

Altered regulation of brain-derived neurotrophic factor protein in hippocampus following slice preparation.

Journal Article Neuroscience · 2004 Brain-derived neurotrophic factor (BDNF) and its cognate receptor tyrosine kinase B (TrkB) play important roles in regulating survival, structure, and function of CNS neurons. One method of studying the functions of these molecules has utilized in vitro hi ... Full text Link to item Cite

Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration.

Journal Article J Neurosci · February 1, 2003 The complement system consists of >30 proteins that interact in a carefully regulated manner to destroy invading bacteria and prevent the deposition of immune complexes in normal tissue. This complex system can be activated by diverse mechanisms proceeding ... Full text Link to item Cite

Temporal specific patterns of semaphorin gene expression in rat brain after kainic acid-induced status epilepticus.

Journal Article Hippocampus · 2003 Mossy fiber sprouting and other forms of synaptic reorganization may form the basis for a recurrent excitatory network in epileptic foci. Four major classes of axon guidance molecules--the ephrins, netrins, slits, and semaphorins--provide targeting informa ... Full text Link to item Cite

Increased expression of brain-derived neurotrophic factor induces formation of basal dendrites and axonal branching in dentate granule cells in hippocampal explant cultures.

Journal Article J Neurosci · November 15, 2002 During limbic epileptogenesis in vivo the dentate granule cells (DGCs) exhibit increased expression of brain-derived neurotrophic factor (BDNF), followed by striking morphologic plasticities, namely the formation of basal dendrites and the sprouting of mos ... Full text Link to item Cite

Fleeting activation of ionotropic glutamate receptors sensitizes cortical neurons to complement attack.

Journal Article Neuron · October 24, 2002 Insidious attack of cortical neurons by complement has been implicated in Alzheimer's and other neurodegenerative diseases. Excitotoxicity, triggered by excessive activation of glutamate receptors, has been implicated in neuronal death following diverse in ... Full text Link to item Cite

Fas(t) balls and Lou Gehrig disease. A clue to selective vulnerability of motor neurons?

Journal Article Neuron · September 12, 2002 The molecular basis of the selective death of motor neurons in amyotrophic lateral sclerosis (ALS) has been an enigma since its description by Charcot in 1869. In this issue of Neuron, demonstrate a motor neuron-specific death pathway which involves Fas an ... Full text Link to item Cite

Immunohistochemical evidence of seizure-induced activation of trkB receptors in the mossy fiber pathway of adult mouse hippocampus.

Journal Article J Neurosci · September 1, 2002 Genetic and pharmacological perturbations suggest that tyrosine receptor kinase B (trkB) receptor activation promotes limbic epileptogenesis, but whether or where trkB activation occurs during epileptogenesis is uncertain. Because activation of trk recepto ... Full text Link to item Cite

B cells and epilepsy: the odd couple.

Journal Article Neurology · March 12, 2002 Full text Link to item Cite

Plasmapheresis in rasmussen's encephalitis

Journal Article Neurology · December 11, 2001 Rasmussen's encephalitis (RE) is a progressive childhood disorder characterized by intractable focal seizures, hemiplegia, dementia, and inflammatory histopathology. The process is typically limited to one cerebral hemisphere. We report four patients with ... Cite

Plasmapheresis in Rasmussen's encephalitis. 1996.

Journal Article Neurology · December 2001 Link to item Cite

Epilepsy and all that jazz.

Journal Article Nat Med · October 2001 Full text Link to item Cite

Synaptic connections from multiple subfields contribute to granule cell hyperexcitability in hippocampal slice cultures.

Journal Article J Neurophysiol · December 2000 Limbic status epilepticus and preparation of hippocampal slice cultures both produce cell loss and denervation. This commonality led us to hypothesize that morphological and physiological alterations in hippocampal slice cultures may be similar to those ob ... Full text Link to item Cite

Autoimmunity to munc-18 in Rasmussen's encephalitis.

Journal Article Neuron · November 2000 Rasmussen's encephalitis (RE) is a rare disease of the central nervous system characterized by severe epileptic seizures, progressive degeneration of a single cerebral hemisphere, and autoimmunity directed against glutamate receptor subunit, GluR3. We repo ... Full text Link to item Cite

GluR3 autoantibodies destroy neural cells in a complement-dependent manner modulated by complement regulatory proteins.

Journal Article J Neurosci · October 1, 2000 GluR3 autoantibodies have been implicated in the development of Rasmussen's encephalitis, a rare neurodegenerative disease of humans characterized by epilepsy and degeneration of a single cerebral hemisphere. GluR3 autoantibodies are found in some Rasmusse ... Full text Link to item Cite

Epilepsy.

Journal Article Neurobiol Dis · October 2000 Full text Link to item Cite

Seizure outcome after temporal lobectomy for temporal lobe epilepsy: a Kaplan-Meier survival analysis.

Journal Article Neurology · February 8, 2000 OBJECTIVE: To determine seizure outcome and its predictors in patients with medically refractory temporal lobe epilepsy (TLE) after temporal lobectomy (TL). BACKGROUND: TL is the most common surgical procedure performed in adolescents and adults for the tr ... Full text Link to item Cite

Immunoglobulin G and complement immunoreactivity in the cerebral cortex of patients with Rasmussen's encephalitis.

Journal Article Neurology · September 11, 1999 OBJECTIVE: To provide evidence that complement (C')-dependent processes may be involved in Rasmussen's encephalitis (RE). BACKGROUND: RE is a rare, progressive, childhood epilepsy syndrome associated with inflammation and neuronal cell loss in a single cer ... Full text Link to item Cite

Emerging insights into the genesis of epilepsy.

Journal Article Nature · June 24, 1999 Epilepsies are a diverse collection of brain disorders that affect 1-2% of the population. Current therapies are unsatisfactory as they provide only symptomatic relief, are effective in only a subset of affected individuals, and are often accompanied by pe ... Full text Link to item Cite

Seizure disorders in mutant mice: relevance to human epilepsies.

Journal Article Curr Opin Neurobiol · June 1999 The rate at which mutant genes producing an epileptic phenotype in mice have been identified over the past few years has been astounding. Manipulating the genome of mice has led to identification of a diversity of genes whose absence or modification either ... Full text Link to item Cite

Immunohistochemical evidence of seizure-induced activation of trk receptors in the mossy fiber pathway of adult rat hippocampus.

Journal Article J Neurosci · June 1, 1999 Recent work suggests that limiting the activation of the trkB subtype of neurotrophin receptor inhibits epileptogenesis, but whether or where neurotrophin receptor activation occurs during epileptogenesis is unclear. Because the activation of trk receptors ... Full text Link to item Cite

Experimental partial epileptogenesis.

Journal Article Curr Opin Neurol · April 1999 Identification of the responsible mutant genes and of the functional consequences of the mutations in experimental preparations have begun to shed light on mechanisms underlying a rare form of partial epilepsy in humans, autosomal dominant nocturnal fronta ... Full text Link to item Cite

Selective inhibition of kindling development by intraventricular administration of TrkB receptor body.

Journal Article J Neurosci · February 15, 1999 Recent work has shown that neurotrophin gene expression is increased after seizures evoked in the kindling model of epilepsy, but whether neurotrophins regulate kindling development is as yet unclear. In this study, we attempted to block selectively the ac ... Full text Link to item Cite

Seizures, cell death, and mossy fiber sprouting in kainic acid-treated organotypic hippocampal cultures.

Journal Article Neuroscience · 1999 Sprouting of the mossy fiber axons of the dentate granule cells is a structural neuronal plasticity found in the mature brain of epileptic humans and experimental animals. Mossy fiber sprouting typically arises in experimental animals after repeated seizur ... Full text Link to item Cite

Autoimmunity and neurological disease: antibody modulation of synaptic transmission.

Journal Article Annu Rev Neurosci · 1999 Over the past three decades, compelling evidence has emerged that the immune system can attack the nervous system with devastating consequences for human health. Either cell-mediated or humoral (antibody-mediated) autoimmune mechanisms may predominate in e ... Full text Link to item Cite

Evaluation of the alpha(2A)-adrenergic receptor gene in a heritable form of temporal lobe epilepsy.

Journal Article Neurology · December 1998 An autosomal dominant form of human temporal lobe epilepsy (TLE) has been mapped to a region of chromosome 10q that contains the intronless alpha(2A)-adrenergic receptor (alpha(2A)AR) gene. Because mutation of the alpha(2A)AR gene in the mouse fosters epil ... Full text Link to item Cite

Measurement of NMDA receptor protein subunits in discrete hippocampal regions of kindled animals.

Journal Article Brain Res Mol Brain Res · October 30, 1998 Kindling refers to a phenomenon in which repeated application of initially subconvulsive electrical stimulations produces limbic and clonic motor seizures of progressively increasing severity. Once established, the increased excitability is lifelong. A div ... Full text Link to item Cite

Increased dentate granule cell neurogenesis following amygdala kindling in the adult rat.

Journal Article Neurosci Lett · May 8, 1998 Structural neuronal network plasticity is associated with epileptogenesis during limbic kindling, but the full extent of network changes is not well understood. We investigated whether dentate granule cell (DGC) neurogenesis, which continues into adulthood ... Full text Link to item Cite

A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine.

Journal Article J Neurosci · March 15, 1998 Norepinephrine serves as a neurotransmitter for a population of neurons the cell bodies of which reside in a brainstem nucleus and the axons of which project widely to discrete subsets of forebrain neurons. Norepinephrine powerfully inhibits epileptogenesi ... Full text Link to item Cite

Kindling and associated mossy fibre sprouting are not affected in mice deficient of NGFI-A/NGFI-B genes.

Journal Article Neuroscience · March 1998 Kindling is an animal model of epileptogenesis, whereby repeated administration of an initially subconvulsive electrical stimulation eventually leads to the development of generalized motor seizures. Once established, the kindling effect is permanent. Alth ... Full text Link to item Cite

Epilepsy genetics: an abundance of riches for biologists.

Journal Article Curr Biol · February 26, 1998 Twenty-five genes have been identified in which mutations cause epileptic seizures in mice. The gene for a Na+/H+ exchanger has recently been found to underlie the spontaneous mutant slow wave epilepsy. Studies of such mutants should help elucidate the mec ... Full text Link to item Cite

Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo.

Journal Article Cell · January 23, 1998 NMDA receptors, a class of glutamate-gated cation channels with high Ca2+ conductance, mediate fast transmission and plasticity of central excitatory synapses. We show here that gene-targeted mice expressing NMDA receptors without the large intracellular C ... Full text Link to item Cite

Glutamate receptor GluR3 antibodies and death of cortical cells.

Journal Article Neuron · January 1998 Rasmussen's encephalitis (RE), a childhood disease characterized by epileptic seizures associated with progressive destruction of a single cerebral hemisphere, is an autoimmune disease in which one of the autoantigens is a glutamate receptor, GluR3. The im ... Full text Link to item Cite

Clinical and electroencephalographic correlates in Rasmussen's encephalitis.

Journal Article Epilepsia · February 1997 PURPOSE: Rasmussen's encephalitis (RE) is a progressive childhood disease characterized by unilateral brain dysfunction, seizures, and inflammatory histopathology. Converging lines of evidence suggest that an autoimmune process is important in the pathogen ... Full text Link to item Cite

Prostaglandin F2alpha is required for NMDA receptor-mediated induction of c-fos mRNA in dentate gyrus neurons.

Journal Article J Neurosci · January 1, 1997 Activation of NMDA receptors has been linked to a diversity of lasting physiological and pathological changes in the mammalian nervous system. The cellular and molecular mechanisms underlying permanent modifications of nervous system structure and function ... Full text Link to item Cite

Disease expression among probands with juvenile myoclonic epilepsy and their family members in two population groups

Journal Article Journal of Epilepsy · December 1, 1996 We report clinical and EEG features of 65 probands with juvenile myoclonic epilepsy (JME) and the occurrence and character of epilepsy among 664 blood relatives of 26 of the 65 probands with a positive family history of seizures. Forty-six families from In ... Full text Cite

NMDA receptor dependence of kindling and mossy fiber sprouting: evidence that the NMDA receptor regulates patterning of hippocampal circuits in the adult brain.

Journal Article J Neurosci · November 15, 1996 The NMDA receptor plays an important role in patterning neural connectivity in the developing brain. In the adult brain, repeated kindling stimulation of limbic pathways increases the NMDA-dependent component of synaptic transmission in granule cells of th ... Full text Link to item Cite

Rasmussen's encephalitis: an autoimmune disorder?

Journal Article Curr Opin Neurobiol · October 1996 Rasmussen's encephalitis is a rare progressive pediatric epileptic syndrome. Recent evidence from experimental animals and patients with the disease suggests an important role for both humoral and cell-mediated immune mechanisms in the pathogenesis of this ... Full text Link to item Cite

Regulation of alternative splicing of NMDAR1 in the kindling model.

Journal Article Brain Res Mol Brain Res · September 5, 1996 Kindling refers to a phenomenon in which repeated application of initially subconvulsive electrical stimulations produces limbic and clonic motor seizures of progressively increasing severity. Once established, the increased excitability is lifelong. Sever ... Full text Link to item Cite

Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures. Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group.

Journal Article Neurology · July 1996 BACKGROUND: Two prospective observations of adults with symptomatic, localization-related (partial) epilepsy included 1,102 patients in VA multicenter studies (VA-118 and VA-264). Analyses assessed the likelihood of remaining seizure free for 12 and 24 mon ... Full text Link to item Cite

Null mutation of c-fos impairs structural and functional plasticities in the kindling model of epilepsy.

Journal Article J Neurosci · June 15, 1996 It has been suggested that expression of the immediate early gene c-fos links fleeting changes in neuronal activity to lasting modifications of neuronal structure and function in the mammalian nervous system. To test this idea, we examined behavioral and e ... Full text Link to item Cite

Rasmussen's encephalitis: an autoimmune disorder?

Journal Article Curr Opin Neurol · April 1996 Rasmussen's encephalitis is a rare progressive pediatric epileptic syndrome. Recent evidence from experimental animals and patients with the disease suggests an important role for both humoral- and cell-mediated immune mechanisms in the pathogenesis of thi ... Link to item Cite

Requirement for superoxide in excitotoxic cell death.

Journal Article Neuron · February 1996 We tested the pathogenic role of O2-) radicals in excitotoxic injury. Inactivation of the TCA cycle enzyme, aconitase, was used as a marker of intracellular O2- levels, and a porphyrin SOD mimetic was used to scavenge O2-. The selective, reversible, and SO ... Full text Link to item Cite

Glutamate receptor autoimmunity in Rasmussen's encephalitis.

Journal Article Cold Spring Harb Symp Quant Biol · 1996 Link to item Cite

Plasmapheresis in Rasmussen's encephalitis.

Journal Article Neurology · January 1996 Rasmussen's encephalitis (RE) is a progressive childhood disorder characterized by intractable focal seizures, hemiplegia, dementia, and inflammatory histopathology. The process is typically limited to one cerebral hemisphere. We report four patients with ... Full text Link to item Cite

Selective enhancement of axonal branching of cultured dentate gyrus neurons by neurotrophic factors.

Journal Article Neuroscience · December 1995 Epileptic seizures in the mature nervous system are associated with axonal sprouting of the hippocampal dentate granule cells and pathological synapse formation. The molecular basis of this morphological rearrangement is obscure. Since epileptic seizures i ... Full text Link to item Cite

Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice.

Journal Article Proc Natl Acad Sci U S A · September 26, 1995 Synapsin I has been proposed to be involved in the modulation of neurotransmitter release by controlling the availability of synaptic vesicles for exocytosis. To further understand the role of synapsin I in the function of adult nerve terminals, we studied ... Full text Link to item Cite

Limbic epilepsy in transgenic mice carrying a Ca2+/calmodulin-dependent kinase II alpha-subunit mutation.

Journal Article Proc Natl Acad Sci U S A · July 18, 1995 Multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMK) phosphorylates proteins pivotally involved in diverse neuronal processes and thereby coordinates cellular responses to external stimuli that regulate intracellular Ca2+ [Hanson, P. I. & Sch ... Full text Link to item Cite

Analyses of the molecular basis of kindling development.

Journal Article Psychiatry Clin Neurosci · June 1995 Kindling has become the most widely studied animal model of limbic epilepsy. Understanding the molecular basis of kindling development may provide novel therapeutic approaches to prevention of limbic epileptogenesis. I briefly describe the kindling model a ... Full text Link to item Cite

Clinical relevance of defects in signalling pathways.

Journal Article Curr Opin Neurobiol · June 1995 This review discusses seven diseases of the human nervous system that have been linked to defects in signal transduction. Recent molecular genetic analyses of rare monogenic disorders have led to the identification of mutant genes in six of the seven disea ... Full text Link to item Cite

N-methyl-D-aspartate receptors activate transcription of c-fos and NGFI-A by distinct phospholipase A2-requiring intracellular signaling pathways.

Journal Article Mol Pharmacol · June 1995 Activation of N-methyl-D-aspartate (NMDA) receptors is required for induction of some lasting changes in nervous system structure and function. The cellular mechanisms involved in transducing receptor stimulation into long-lasting changes in cellular activ ... Link to item Cite

Differences in the anatomic distribution of immediate-early gene expression in amygdala and angular bundle kindling development.

Journal Article J Neurosci · March 1995 Kindling is a model in which fleeting changes of neuronal activity produce a lifelong modification of neuronal structure and function in the mature nervous system. Immediate-early genes (IEGs) such as c-fos have been implicated as a causal link in the chai ... Full text Link to item Cite

c-fos: An epiphenomenon or causal link in mossy fiber sprouting and kindling

Journal Article Journal of the Japan Epilepsy Society · January 1, 1995 Cite

Autoantibodies to glutamate receptor GluR3 in Rasmussen's encephalitis.

Journal Article Science · July 29, 1994 Rasmussen's encephalitis is a progressive childhood disease of unknown cause characterized by severe epilepsy, hemiplegia, dementia, and inflammation of the brain. During efforts to raise antibodies to recombinant glutamate receptors (GluRs), behaviors typ ... Full text Link to item Cite

Kindling induces the long-lasting expression of a novel population of NMDA receptors in hippocampal region CA3.

Journal Article J Neurosci · July 1994 Kindling refers to a phenomenon in which repeated application of initially subconvulsive electrical stimulations produces limbic and clonic motor seizures of progressively increasing severity. Once established, the increased excitability is lifelong. Enhan ... Full text Link to item Cite

A physical map across chromosome 11q22-q23 containing the major locus for ataxia telangiectasia.

Journal Article Genomics · June 1994 We have constructed a long-range physical map for 12 markers, including genes for GRIA4, IL1BC, and ACAT, across 9 Mb of chromosome 11q22-q23 in the region of the major locus for ataxia-telangiectasia (A-T). The markers fall into proximal and distal groups ... Full text Link to item Cite

Kindling reduces sensitivity of CA3 hippocampal pyramidal cells to competitive NMDA receptor antagonists.

Journal Article Neuropharmacology · February 1994 Kindling is a form of experimental epilepsy in which periodic electrical stimulation of a brain pathway induces a permanently hyperexcitable state. A previous study demonstrated that kindling enhances the sensitivity of hippocampal CA3 pyramidal cells to N ... Full text Link to item Cite

Identification of genetic defect of an epilepsy: strategies for therapeutic advances.

Journal Article Epilepsia · 1994 Advances in molecular genetics and molecular biology are transforming the biology of human disease. Cures for diseases previously refractory to all treatments have become the reality for some disorders and the legitimate promise for others. In the case of ... Full text Link to item Cite

Mechanism of epilepsy.

Journal Article Annu Rev Med · 1994 Epilepsy is a collection of diverse disorders that together affect approximately 1% of the general population. Current therapies are largely symptomatic and are aimed at controlling seizures in affected individuals. This review focuses on emerging insights ... Full text Link to item Cite

Introduction and Symposium Overview

Journal Article Epilepsia · January 1, 1994 Full text Cite

Panel discussion

Journal Article Epilepsia · January 1, 1994 Full text Cite

Panel discussion

Journal Article Epilepsia · January 1, 1994 Full text Cite

ANTIEPILEPTIC DRUGS - OPTIMAL USE AND FUTURE-PROSPECTS

Journal Article EPILEPSIA · January 1, 1994 Link to item Cite

Chromosomal localization of gene for human glutamate receptor subunit-7.

Journal Article Somat Cell Mol Genet · November 1993 We isolated a human glutamate receptor subunit 7 (GluR-7) cosmid after high stringency screening of a human genomic placental library using a rat GluR-7 cDNA as a probe. A 614-bp fragment of the GluR-7 cosmid was sequenced, and an exon that encodes 53 amin ... Full text Link to item Cite

Excitatory amino acid receptors and epilepsy.

Journal Article Curr Opin Neurol Neurosurg · August 1993 The rapid pace of discovery in the molecular biology of glutamate receptors includes advances concerning the N-methyl-D-aspartate receptor. New information emerging in this area is already affecting the study of epilepsy in animal models and provides novel ... Link to item Cite

Cloning and expression of a novel Na(+)-dependent neutral amino acid transporter structurally related to mammalian Na+/glutamate cotransporters.

Journal Article J Biol Chem · July 25, 1993 A cDNA has been isolated from human hippocampus that appears to encode a novel Na(+)-dependent, Cl(-)-independent, neutral amino acid transporter. The putative protein, designated SATT, is 529 amino acids long and exhibits significant amino acid sequence i ... Link to item Cite

Induction of c-fos mRNA by kindled seizures: complex relationship with neuronal burst firing.

Journal Article J Neurosci · February 1993 Expression of the immediate-early gene c-fos has been advanced as a marker of neuronal activity in the adult nervous system. We sought to test the validity of c-fos mRNA expression as a marker of neuronal activity during seizures and to elucidate specific ... Full text Link to item Cite

Pulmonary follow-up 2.5 years after a randomized, controlled, multiple dose bovine surfactant study of preterm newborn infants.

Journal Article Pediatric pulmonology · 1993 Forty-seven preterm infants, who were previously enrolled in a prospective, randomized, blinded study at birth to assess the effects of multiple doses of exogenous bovine surfactant to prevent respiratory distress syndrome, underwent lung function evaluati ... Cite

Ionotropic glutamate receptor subtypes activate c-fos transcription by distinct calcium-requiring intracellular signaling pathways.

Journal Article Neuron · January 1993 N-Methyl-D-aspartate (NMDA) or non-NMDA receptor activation is sufficient to induce transcription of the immediate early gene c-fos in a calcium-requiring manner. We sought to determine whether the calcium-dependent mechanisms inducing c-fos transcription ... Full text Link to item Cite

The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21.1-22.1 in the vicinity of the gene for familial amyotrophic lateral sclerosis.

Journal Article Proc Natl Acad Sci U S A · January 1, 1993 Genomic clones of the human non-N-methyl-D-aspartate (non-NMDA) glutamate receptor subunit GluR5 were isolated by high-stringency screening of a cosmid library using the rat cDNA as a probe. The chromosomal localization of the human GluR5 gene has been est ... Full text Link to item Cite

The neurobiological basis of epilepsy.

Journal Article Trends Neurosci · October 1992 Full text Link to item Cite

NMDA and non-NMDA receptor-mediated increase of c-fos mRNA in dentate gyrus neurons involves calcium influx via different routes.

Journal Article J Neurosci · August 1992 We examined the effects of selective agonists of ionotropic excitatory amino acid (EAA) receptor subtypes on induction of the immediate early gene c-fos. We used in situ hybridization to measure c-fos mRNA and fura-2 imaging to measure intracellular calciu ... Full text Link to item Cite

Chromosomal localization of human glutamate receptor genes.

Journal Article J Neurosci · July 1992 The chromosomal localization of human glutamate receptor genes (GluR1-4) has been established using PCR with DNA isolated from mapping panels of Chinese hamster-human hybrid cell lines and high-resolution fluorescent in situ suppression hybridization. This ... Full text Link to item Cite

Kindling enhances sensitivity of CA3 hippocampal pyramidal cells to NMDA.

Journal Article J Neurosci · May 1992 Kindling is a form of experimental epileptogenesis in which periodic electrical stimulation of a brain pathway induces a permanently hyperexcitable state. Previous studies suggested that kindling might be explained, at least in part, by an increased sensit ... Full text Link to item Cite

Differential expression of immediate early genes in the hippocampus in the kindling model of epilepsy.

Journal Article Brain Res Mol Brain Res · September 1991 Kindling is a phenomenon in which brief afterdischarges (ADs) evoked by periodic electrical stimulation of the brain eventually result in generalized clonic motor seizures. Once present, the enhanced sensitivity to electrical stimulation is lifelong. The m ... Full text Link to item Cite

Activation of substantia nigra pars reticulata neurons: role in the initiation and behavioral expression of kindled seizures.

Journal Article Brain Res · April 5, 1991 Numerous studies have implicated the substantia nigra pars reticulata (SNR) in the initiation and behavioral expression of kindled seizures. In immobilized, amygdala-kindled animals, SNR neurons have been shown to enter an intense burst-firing pattern duri ... Full text Link to item Cite

Antiepileptogenic effects of conventional anticonvulsants in the kindling model of epilespy.

Journal Article Ann Neurol · April 1991 We sought to determine whether the clinically effective anticonvulsant drug valproate exhibited antiepileptogenic properties in the kindling model (we use the term anticonvulsant to mean suppression of seizure, and antiepileptogenic to mean suppression of ... Full text Link to item Cite

Increased AMPA-sensitive quisqualate receptor binding and reduced NMDA receptor binding in epileptic human hippocampus.

Journal Article J Neurosci · February 1991 Based on results from the kindling model of epilepsy, we hypothesized that enhanced binding of radioligands to the NMDA receptor and decreased binding to the alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA)-sensitive quisqualate (ASQ) receptor ... Full text Link to item Cite

Decreased density, but not number, of N-methyl-D-aspartate, glycine and phencyclidine binding sites in hippocampus of senescent rats.

Journal Article Brain Res · November 5, 1990 Aging is associated with reduced rates of kindling and spatial learning. Blockade of N-methyl-D-aspartate (NMDA) receptors in young animals produces effects similar to those of aging. These findings raise the possibility that age-dependent reductions in ne ... Full text Link to item Cite

Induction of c-fos mRNA expression by afterdischarge in the hippocampus of naive and kindled rats.

Journal Article J Neurochem · September 1990 Periodic induction of focal electrical seizure [afterdischarge (AD)] is an absolute prerequisite for the development of kindling, an animal model of complex partial epilepsy. Once established, it is a permanent condition. The mechanism(s) that translate AD ... Full text Link to item Cite

Excitatory amino acid receptors in epilepsy.

Journal Article Trends Pharmacol Sci · August 1990 Excitatory amino acid transmitters participate in normal synaptic transmission throughout the CNS (see Headley and Grillner, May TiPS), so it comes as no surprise that such excitatory pathways are involved in the initiation of seizures and their propagatio ... Full text Link to item Cite

Evidence that zinc inhibits N-methyl-D-aspartate receptor-gated ion channel activation by noncompetitive antagonism of glycine binding.

Journal Article Mol Pharmacol · July 1990 Zinc noncompetitively antagonizes N-methyl-D-aspartate (NMDA) receptor-mediated responses in cultured neurons. We investigated the mechanism of this inhibition by examining the effect of zinc on ligand binding to three distinct sites on the NMDA receptor i ... Link to item Cite

Biochemical and radiohistochemical analyses of alpha-2 adrenergic receptors in the kindling model of epilepsy.

Journal Article J Pharmacol Exp Ther · June 1990 Biochemical and radiohistochemical methods were used to study alterations in alpha-2 adrenergic receptors in the kindling model of epilepsy. The radioligands used for antagonist and agonist binding were [3H]idazoxan and [3H]p-aminoclonidine, respectively. ... Link to item Cite

A radiohistochemical measure of [3H]TCP binding to the activated NMDA-receptor-gated ion channel in rat brain.

Journal Article Brain Res · May 21, 1990 The N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptor is linked to an ion channel that is blocked by the phencyclidine analog N-(1-[thienyl]cyclohexyl)piperidine (TCP). Previous studies have shown that NMDA and glycine act together to i ... Full text Link to item Cite

Inhibition of muscarinic-coupled phosphoinositide hydrolysis by N-methyl-D-aspartate is dependent on depolarization via channel activation.

Journal Article J Neurochem · May 1990 The intent of this work was to elucidate the mechanism by which N-methyl-D-aspartate (NMDA) receptor agonists inhibit a second messenger system, namely, the stimulation of phosphoinositide (PI) hydrolysis activated by muscarinic cholinergic receptor agonis ... Full text Link to item Cite

Anterior temporal lobectomy for complex partial seizures: evaluation, results, and long-term follow-up in 100 cases.

Journal Article Neurology · March 1990 We report evaluation and results in 100 patients who had undergone anterior temporal lobectomy for intractable complex partial seizures. Average follow-up was 9.0 years (range, 2 to 21 years). In the 2nd postoperative year, 63% were seizure free, 16% were ... Full text Link to item Cite

Kainate and quisqualate receptor autoradiography in rat brain after angular bundle kindling.

Journal Article Neuroscience · 1990 The kainate and quisqualate types of excitatory amino acid receptor were visualized autoradiographically in brain sections from rats kindled by stimulating the angular bundle. Kainate receptors were labeled with [3H]kainate and quisqualate receptors with L ... Full text Link to item Cite

Kindling, prenatal exposure to ethanol and postnatal development selectively alter responses of hippocampal pyramidal cells to NMDA.

Journal Article Adv Exp Med Biol · 1990 Our studies suggest that treatments, such as kindling and exposure to ethanol in utero, which produce irreversible pathological changes in brain function also selectively alter neuronal responses to NMDA. We have identified increases in agonist potency, wh ... Full text Link to item Cite

Basic mechanisms of the epilepsies

Journal Article Current Opinion in Neurology and Neurosurgery · January 1, 1990 Cite

Effect of kindling on potassium-induced electrographic seizures in vitro.

Journal Article Neurosci Lett · November 6, 1989 The properties of high [K+]o-induced spontaneous bursting and electrographic seizures in hippocampal slices prepared from rats subjected to kindling from either the lateral entorhinal cortex or the angular bundle were compared to those in control slices. K ... Full text Link to item Cite

Intravenous phenytoin is an effective anticonvulsant in the kindling model.

Journal Article Ann Neurol · November 1989 We reexamined the efficacy of the clinically effective anticonvulsant drug phenytoin in the kindling model. We investigated the effects of varying doses of intravenous phenytoin on serum concentrations and on several indexes of stimulation-evoked kindled s ... Full text Link to item Cite

N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex.

Journal Article Proc Natl Acad Sci U S A · October 1989 Kindling is an animal model of epilepsy and neuronal plasticity produced by periodic electrical stimulation of the brain. Electrophysiologic studies indicate that this phenomenon is associated with increased participation of N-methyl-D-aspartate (NMDA) rec ... Full text Link to item Cite

Biochemical evidence for enhanced sensitivity to N-methyl-D-aspartate in the hippocampal formation of kindled rats.

Journal Article Brain Res · September 4, 1989 The inhibitory effect of N-methyl-D-aspartate (NMDA) upon carbachol-stimulated phosphoinositide (PI) hydrolysis was studied in transverse hippocampal slices prepared from control and amygdaloid kindled rats. Kindling significantly increased the inhibitory ... Full text Link to item Cite

Effects of intranigral application of clinically-effective anticonvulsants on electroshock-induced seizures.

Journal Article Neuropharmacology · August 1989 The authors sought to determine whether focal application of clinically-effective anticonvulsants to the substantia nigra produced anticonvulsant effects. To this end, the effects of phenobarbital, carbamazepine and phenytoin were examined on the electrosh ... Full text Link to item Cite

Glycine regulation of the N-methyl-D-aspartate receptor-gated ion channel in hippocampal membranes.

Journal Article Mol Pharmacol · August 1989 The N-methyl-D-aspartate receptor-gated ion channel (NMDA channel) is regulated by glycine. To examine the interaction of glycine and NMDA receptor ligands on NMDA channel function, we used a biochemical marker of channel opening, [3H]N-(1-[thienyl]cyclohe ... Link to item Cite

Time course of carbamazepine autoinduction. The VA Cooperative Study No.118 Group.

Journal Article Neurology · April 1989 We sequentially determined carbamazepine clearance values in 17 patients at the end of weeks 1, 2, 4, 8, and 12 of monotherapy. There were no significant differences among these clearance values. In 11 of 17 patients, week 1 clearance accurately predicted ... Full text Link to item Cite

Barbiturate-related connective tissue disorders.

Journal Article Arch Intern Med · April 1989 Development of Dupuytren's contractures, frozen shoulder, Ledderhose's syndrome, Peyronie's disease, fibromas, and general joint pain has been linked in retrospective studies and case reports to the use of antiepileptic drugs. We undertook a prospective su ... Link to item Cite

N-methyl-D-aspartate receptor autoradiography in rat brain after angular bundle kindling.

Journal Article Brain Res · March 20, 1989 The specific binding of L-[3H]glutamate to N-methyl-D-aspartate (NMDA) receptors in brain regions of kindled rats was visualized autoradiographically and quantitated. When assayed 28 days after the last evoked seizure, NMDA receptor binding had declined by ... Full text Link to item Cite

Development of new pharmacological agents for epilepsy: lessons from the kindling model.

Journal Article Epilepsia · 1989 The greatest value of the kindling model for new therapy of epilepsy almost certainly lies in elucidating the molecular basis of its development and persistence. Such an understanding may provide a foundation for therapies aimed at prevention or perhaps ev ... Full text Link to item Cite

TCP binding: a tool for studying NMDA receptor-mediated neurotransmission in kindling.

Journal Article Neurosci Biobehav Rev · 1989 Findings from numerous pharmacological and electrophysiological studies have uniquely implicated the N-methyl-D-aspartate (NMDA) receptor in kindling. Recent findings indicate that this receptor is regulated by ligands acting at both amino acid (NMDA and g ... Link to item Cite

Novel approach to studying N‐methyl‐D‐aspartate receptor function in the kindling model of epilepsy

Journal Article Drug Development Research · January 1, 1989 Kindling is the most widely studied animal model of epilepsy. This manuscript reviews studies of the role of N‐methyl‐D‐aspartate (NMDA) receptors in the kindling model. Pharmacologic studies suggest that 1) NMDA receptor activation contributes to the deve ... Full text Cite

Microinjection of muscimol into entopeduncular nucleus suppresses pilocarpine but not maximal electroshock seizures in rats.

Journal Article Brain Res · October 18, 1988 Microinjection of muscimol (406 pmol) into the rat entopeduncular nucleus, the analogue of the primate globus pallidus pars interna, significantly suppressed pilocarpine but not maximal electroshock seizures in a spatially specific manner. In contrast to i ... Full text Link to item Cite

N-methyl-D-aspartate receptor regulation of uncompetitive antagonist binding in rat brain membranes: kinetic analysis.

Journal Article Mol Pharmacol · September 1988 N-Methyl-D-aspartate (NMDA) receptor ligands regulate the binding of uncompetitive antagonists in membranes prepared from rat brain. To determine the mechanism of this regulation, we examined the kinetics of the binding of the radiolabeled uncompetitive an ... Link to item Cite

Abnormal hyperexcitability of hippocampal slices from kindled rats is transient.

Journal Article Brain Res · June 21, 1988 The anatomic substrates and mechanisms responsible for the development and permanence of kindling remain to be determined. One region believed to play an important role in kindling development is the hippocampus. Epileptiform activity (K+-induced spontaneo ... Full text Link to item Cite

Anticonvulsant and antiepileptogenic actions of MK-801 in the kindling and electroshock models.

Journal Article Neuropharmacology · June 1988 The actions of MK-801, a noncompetitive antagonist at the N-methyl-d-aspartate subtype of excitatory amino acid receptor, were investigated on the development of kindling and on seizures in the electroshock and kindling models. The drug MK-801 potently and ... Full text Link to item Cite

Anticonvulsant action of intranigral gamma-vinyl-GABA: role of nonadrenergic neurotransmission.

Journal Article Brain Res · January 12, 1988 Intranigral gamma-vinyl-GABA (GVG) suppresses electroshock seizures (ES). This anticonvulsant action was blocked by systemic treatment with the alpha 2-antagonist idazoxan. Consequently, we tested the idea that intranigral GABA mimetics suppress ES by incr ... Full text Link to item Cite

Pursuit of the mechanisms of kindling.

Journal Article Trends Neurosci · January 1988 Full text Link to item Cite

Microinjection of a benzodiazepine into substantia nigra elevates kindled seizure threshold.

Journal Article Brain Res · October 13, 1987 The purpose of these experiments was to initiate investigations of the brain site(s) at which the benzodiazepines exert their anticonvulsant effect. We examined the effects of microinjections of clonazepam into substantia nigra (SN) on seizure threshold in ... Full text Link to item Cite

Causes of treatment failure with antiepileptic drugs vary over time.

Journal Article Neurology · October 1987 The V.A. Epilepsy Cooperative Study Group evaluated monotherapy with carbamazepine, phenobarbital, phenytoin, and primidone in a total of 622 patients with previously untreated partial seizures. In the 24 months following onset of treatment, 223 patients f ... Full text Link to item Cite

An in vitro autoradiographic analysis of mu and delta opioid binding in the hippocampal formation of kindled rats.

Journal Article Brain Res · June 2, 1987 Recent studies have shown that opioid peptide levels are altered in hippocampal formation of kindled animals. We therefore studied the distributions of mu and delta opioid binding sites in hippocampal formation of kindled and control rats using quantitativ ... Full text Link to item Cite

The role of substantia nigra in the development of kindling: pharmacologic and lesion studies.

Journal Article Brain Res · June 2, 1987 The role of substantia nigra (SN) in the development of kindling was investigated. Microinjection of gamma-vinyl gamma-aminobutyric acid (GVG), a gamma-aminobutyric acid (GABA) transaminase inhibitor, into the SN bilaterally retarded kindling development b ... Full text Link to item Cite

Evidence implicating alpha-2 adrenergic receptors in the anticonvulsant action of intranigral muscimol.

Journal Article J Pharmacol Exp Ther · June 1987 The effects of systemically administered catecholamine receptor antagonists on the anticonvulsant action produced by local application of a gamma-aminobutyric acid agonist, muscimol, to the substantia nigra of rats were studied. Both electroshock and kindl ... Link to item Cite

Alpha-2 receptors mediate an endogenous noradrenergic suppression of kindling development.

Journal Article J Pharmacol Exp Ther · June 1987 We sought to elucidate the receptor subtype through which endogenous norepinephrine suppresses epileptogenesis in the rat kindling model. To this end we examined the effects of systemically administered selective antagonists and an alpha-2 agonist on kindl ... Link to item Cite

Stimulation of substantia nigra pars reticulata enhances dentate granule cell excitability.

Journal Article Brain Res · May 12, 1987 We studied the effects of electrical and chemical stimulation of the substantia nigra (SN) on the dentate granule cell (DGC) response to perforant path stimulation. Studies were carried out in both pentobarbital anesthetized and awake freely moving rats. C ... Full text Link to item Cite

Activity of locus coeruleus neurons in amygdala kindled rats: role in the suppression of afterdischarge.

Journal Article Brain Res · March 24, 1987 Kindling is a model of epilepsy. The mechanisms of kindling development are unknown but may involve attenuation of noradrenergic neurotransmission. Single unit recordings, pharmacologic and lesion techniques were used to test the hypothesis that the increa ... Full text Link to item Cite

Intranigral dynorphin-1-13 suppresses kindled seizures by a naloxone-insensitive mechanism.

Journal Article Brain Res · March 10, 1987 Numerous lines of evidence indicate that the substantia nigra (SN) facilitates the propagation of seizures in kindling and in other seizure models. Intranigral injection of dynorphin-1-13 exerted a potent seizure suppressant action in kindled rats. This se ... Full text Link to item Cite

Anti-seizure and anti-epileptogenic effect of gamma-vinyl gamma-aminobutyric acid in amygdaloid kindling.

Journal Article Brain Res · November 29, 1986 We examined the effects of systemic administration of gamma-vinyl gamma-aminobutyric acid (GVG), a gamma-aminobutyric acid (GABA) transaminase inhibitor, on the kindling model of epilepsy in rats. GVG (1200 or 1500 mg/kg) approximately doubled the number o ... Full text Link to item Cite

Activation of substantia nigra neurons: role in the propagation of seizures in kindled rats.

Journal Article J Neurosci · October 1986 The substantia nigra (SN) is crucial to the propagation of seizures in kindled rats and in other experimental seizure models. However, the mechanisms by which the SN acts to facilitate the propagation of seizures are unknown. To investigate these mechanism ... Full text Link to item Cite

Method of lesioning brainstem determines seizure probability.

Journal Article J Neurosci Methods · September 1986 We examined 3 different methods of brainstem lesioning to assess their propensities to evoke seizures in the early postoperative period. Lesioning by electrolysis or microinjection of the neurotoxin, N-methyl-D,L-aspartate, caused seizures, but lesioning b ... Full text Link to item Cite

Quantitative autoradiographic analysis of mu and delta opioid binding sites in the rat hippocampal formation.

Journal Article J Comp Neurol · April 8, 1986 The distributions of mu and delta opioid binding sites were studied in rat hippocampal formation by using quantitative in vitro autoradiography. Mu binding sites, labeled with 125I-FK-33824, showed a highly organized laminar distribution. Binding was great ... Full text Link to item Cite

Evidence implicating dentate granule cells in wet dog shakes produced by kindling stimulations of entorhinal cortex.

Journal Article Exp Neurol · April 1986 We studied the occurrence of wet dog shakes during the evolution of kindling induced by electrical stimulation of the lateral entorhinal cortex. Wet dog shakes occur with high incidence, particularly early in development of kindling. We also demonstrated t ... Full text Link to item Cite

Evidence implicating dentate granule cells in development of entorhinal kindling.

Journal Article Exp Neurol · April 1986 Kindling is an animal model of epilepsy induced by periodic focal electrical stimulation of the brain. The network of brain structures responsible for this permanent abnormal excitability is unknown. We hypothesized that the hippocampal formation serves a ... Full text Link to item Cite

Changes in dynorphin, enkephalin and cholecystokinin content of hippocampus and substantia nigra after amygdala kindling.

Journal Article Brain Res · February 12, 1986 Amygdaloid kindling of rats produced an increase in hippocampal Met5-enkephalin-Arg6-Gly7-Leu8 and cholecystokinin immunoreactivities and simultaneously a decrease in dynorphin A1-8 content. In substantia nigra Met5-enkephalin-Arg6-Gly7-Leu8 was increased ... Full text Link to item Cite

Effects of age on kindling and kindled seizure-induced increase of benzodiazepine receptor binding.

Journal Article Brain Res · January 1, 1986 We examined the effects of age on kindled seizure development, benzodiazepine receptor binding, and kindled seizure-induced increases of benzodiazepine receptor binding. The results disclosed that: development of kindling required greater numbers of stimul ... Full text Link to item Cite

Interstitial ion concentrations and paroxysmal discharges in hippocampal formation and spinal cord.

Journal Article Adv Neurol · 1986 This chapter contains a summary of previous work, as well as some new data concerning the roles of potassium and calcium in electrically and chemically induced seizures. During tonic-clonic seizure discharges, the extracellular concentration of potassium, ... Link to item Cite

Kindling model of epilepsy.

Journal Article Adv Neurol · 1986 Kindling is an animal model of epilepsy produced by focal electrical stimulation of the brain. This chapter: describes the kindling phenomenon; considers the validity of kindling as an animal model and proposes a hypothesis as to how kindling might contrib ... Link to item Cite

Abnormal neuronal excitability in hippocampal slices from kindled rats.

Journal Article J Neurophysiol · November 1985 To determine if electrophysiological properties of hippocampal pathways are altered in kindled rats, extracellular recordings were made from hippocampal slices of rats kindled in the lateral entorhinal cortex and compared with those from implanted but unst ... Full text Link to item Cite

gamma-Aminobutyric acid and benzodiazepine receptors in the kindling model of epilepsy: a quantitative radiohistochemical study.

Journal Article J Neurosci · October 1985 Quantitative radiohistochemistry was utilized to study alterations of gamma-aminobutyric acid (GABA) and benzodiazepine receptors in the kindling model of epilepsy. The radioligands used for GABA and benzodiazepine receptors were [3H] muscimol and [3H]flun ... Full text Link to item Cite

Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures.

Journal Article N Engl J Med · July 18, 1985 We conducted a 10-center, double-blind trial to compare the efficacy and toxicity of four antiepileptic drugs in the treatment of partial and secondarily generalized tonic-clonic seizures in 622 adults. Patients were randomly assigned to treatment with car ... Full text Link to item Cite

Autoradiographic localization of benzomorphan binding sites in rat brain.

Journal Article Eur J Pharmacol · July 17, 1985 The benzomorphan subpopulation of opiate binding sites was labeled by [3H]diprenorphine in the presence of unlabeled ligands selected to quench mu and delta opiate binding sites. The distribution of benzomorphan binding sites was then localized autoradiogr ... Full text Link to item Cite

Sustained potential shifts and paroxysmal discharges in hippocampal formation.

Journal Article J Neurophysiol · April 1985 Paroxysmal firing was provoked by electric stimulation of afferent pathways in hippocampal formation of intact, urethan-anesthetized rats, of freely moving unanesthetized rats, and in hippocampal tissue slices in vitro. The electric responses of fascia den ... Full text Link to item Cite

Knife cuts of entorhinal cortex: effects on development of amygdaloid kindling and seizure-induced decrease of muscarinic cholinergic receptors.

Journal Article J Neurosci · February 1985 This report examines the effect of transection of the entorhinal hippocampal projection on amygdaloid kindling. We found that: bilateral knife cuts of entorhinal cortex but not of dorsal neocortex antagonize the development of amygdaloid kindling; and bila ... Full text Link to item Cite

Comparison of the effects of diphenylbarbituric acid, phenobarbital, pentobarbital and secobarbital on GABA-mediated inhibition and benzodiazepine binding.

Journal Article J Pharmacol Exp Ther · January 1985 We utilized biochemical and electrophysiological methods to compare the effects of anesthetic and anticonvulsant barbiturates on gamma-aminobutyric acid (GABA) receptor-coupled responses. Biochemical analysis involved barbiturate regulation of the affinity ... Link to item Cite

The kindling model of epilepsy: a critical review.

Journal Article CRC Crit Rev Clin Neurobiol · 1985 Kindling is an animal model of epilepsy induced by electrical stimulation of the brain. This model has attracted the interest of many neuroscientists, in part because it involves a robust, permanent modification of brain function. This report will describe ... Link to item Cite

Reduced kainic acid binding in rat hippocampal formation after limbic kindling.

Journal Article Brain Res · December 3, 1984 The specific binding of [3H]kainic acid to hippocampal membranes was examined autoradiographically in rats kindled by tetanic stimulation of the amygdala or angular bundle. One day after the last of 3 class 4-5 kindled seizures, the specific binding of [3H ... Full text Link to item Cite

Lateral entorhinal cortical kindling can be established without potentiation of the entorhinal-granule cell synapse.

Journal Article Exp Neurol · December 1984 Kindling is an animal model of epilepsy which involves a permanently enhanced neuronal response to an electrical stimulus. It has been proposed that long-term potentiation (LTP) of excitatory synaptic transmission is the cellular basis of kindling. Therefo ... Full text Link to item Cite

Evidence implicating substantia nigra in regulation of kindled seizure threshold.

Journal Article J Neurosci · September 1984 We studied the effects of microinjected drugs and brainstem lesions on motor and limbic seizures in the kindling model of epilepsy. The duration of motor seizures was determined by timing the colonic and tonic movements of the extremities. The duration of ... Full text Link to item Cite

Selective and reversible increase in the number of quisqualate-sensitive glutamate binding sites on hippocampal synaptic membranes after angular bundle kindling.

Journal Article Brain Res · July 30, 1984 The specific binding of L-[3H]glutamate to hippocampal synaptic membranes was examined in rats kindled by tetanic stimulation of the angular bundle. One day after the last of a minimum of 3 class 4 kindled seizures, the binding of L-[3H]glutamate to a quis ... Full text Link to item Cite

Role of neurotransmitters in seizure mechanisms in the kindling model of epilepsy.

Journal Article Fed Proc · July 1984 The molecular basis of the abnormal excitability of the kindling phenomenon is unclear. The alterations of neurotransmitters and their receptors identified in this model most likely underlie the brain's response to repetitive neuronal firing during seizure ... Link to item Cite

Kindling: an animal model of complex partial epilepsy.

Journal Article Ann Neurol · 1984 Kindling is an animal model of complex partial epilepsy induced by focal electrical stimulation of the brain. This paper describes the phenomenon and underscores the limited nature of current insights into its basic mechanisms. Anatomical delineation of th ... Full text Link to item Cite

Kindled seizure-induced reduction of muscarinic cholinergic receptors in rat hippocampal formation: evidence for localization to dentate granule cells.

Journal Article J Comp Neurol · November 20, 1983 The binding of [3H] quinuclidinyl benzilate ( [3H] QNB) to muscarinic cholinergic receptors in dentate gyrus of rat hippocampal formation was analyzed by membrane binding assay and in vitro autoradiography. The destruction of dentate granule cells, either ... Full text Link to item Cite

Benzodiazepine receptor declines in hippocampal formation following limbic seizures.

Journal Article Brain Res · October 31, 1983 Electrolytic lesions of entorhinal cortex have previously been shown to consistently produce limbic seizures. We report a bilateral and symmetrical decline in benzodiazepine receptor number in dentate gyrus of the hippocampal formation in unilateral entorh ... Full text Link to item Cite

Kindled seizures result in decreased responsiveness of benzodiazepine receptors to gamma-aminobutyric acid (GABA).

Journal Article J Pharmacol Exp Ther · July 1983 Repeated kindled seizures result in increased numbers of benzodiazepine receptors in fascia dentata membranes. Our previous work localized these receptors to a discrete neuronal population, the dentate granule cells. The present investigation characterizes ... Link to item Cite

83 OPIOID RECEPTORS IN HIPPOCAMPAL FORMATION IN THE KINDLING MODEL OF TEMPORAL LOBE EPILEPSY

Journal Article Journal of Neuropathology and Experimental Neurology · May 1983 Full text Cite

A design for the prospective evaluation of the efficacy and toxicity of antiepileptic drugs in adults.

Journal Article Neurology · March 1983 The design for the comparative evaluation of the efficacy and toxicity of phenobarbital, phenytoin, primidone, and carbamazepine is outlined. A double-blind prospective study of a sufficient number of patients can determine the optimum drug to use initiall ... Full text Link to item Cite

Pseudoepileptic seizures: methods and video analysis to aid diagnosis.

Journal Article Ann Neurol · November 1982 The purposes of this study were to obtain a detailed description of the clinical features of pseudoepileptic (PE) seizures, to try to reproduce these events in the laboratory during a single recording, and to establish a framework useful to the clinician f ... Full text Link to item Cite

Kindled seizures selectively reduce a subpopulation of [3H]quinuclidinyl benzilate binding sites in rat dentate gyrus.

Journal Article J Pharmacol Exp Ther · September 1982 Amygdala-kindled seizures reduced significantly the total number of [3H]quinuclidinyl benzilate binding sites in both dentate and hippocampal gyri compared to electrode implanted unstimulated controls. Both high and low affinity carbachol displaceable bind ... Link to item Cite

Intradentate colchicine retards the development of amygdala kindling.

Journal Article Ann Neurol · April 1982 The mechanisms underlying the kindling model of epilepsy are unknown. Presumably, an altered network of neural circuits underlie amygdala kindling. Biochemical and radiohistochemical studies have pointed to the dentate granule cells (DGC) of the hippocampa ... Full text Link to item Cite

Seizures down-regulate muscarinic cholinergic receptors in hippocampal formation.

Journal Article Brain Res · March 11, 1982 Muscarinic cholinergic receptors (MCR) have been previously shown to decline in the hippocampal formation (HPF) of amygdala-kindled rats. Seizures have been proposed as the process responsible for this down-regulation. We now demonstrate similar down-regul ... Full text Link to item Cite

Electrolytic entorhinal lesions cause seizures.

Journal Article Brain Res · January 14, 1982 The entorhinal cortex is a key site of interneuronal communication between a variety of cortical and subcortical areas and hippocampal formation. Lesioning the entorhinal cortex is commonly used in studies of the hippocampal formation, animal behavior and ... Full text Link to item Cite

Benzodiazepine receptor increases after repeated seizures: evidence for localization to dentate granule cells.

Journal Article Proc Natl Acad Sci U S A · January 1982 Repeated seizures, whether induced by kindling or electroshock, result in increased numbers of benzodiazepine receptors in hippocampal formation membranes. We sought to determine the cellular constituents containing the receptor increases. Binding studies ... Full text Link to item Cite

Epilepsy.

Journal Article Proc Annu Meet Med Sect Am Counc Life Insur · 1981 Link to item Cite

DETECTION AND MECHANISMS OF ARRHYTHMOGENIC EPILEPSY - REPLY

Journal Article AMERICAN HEART JOURNAL · 1981 Full text Cite

Effects of oral choline on human complex partial seizures.

Journal Article Neurology · December 1980 We carried out an open study of the effects of large doses (12 to 16 gm per day) of oral choline on medically intractable human complex partial seizures (CPS). Marked increases of plasma choline concentration (75 to 300%) in three subjects were associated ... Full text Link to item Cite

Arrhythmogenic epilepsy: an hypothesis.

Journal Article Am Heart J · November 1980 This report describes a clinical syndrome of arrhythmias that may have neural origin. Two patients presented with episodes of loss of consciousness, disorientation, and paroxysmal supraventricular tachycardia (PSVT). One patient reported experiencing neuro ... Full text Link to item Cite

Evidence for an agonist independent down regulation of hippocampal muscarinic receptors in kindling.

Journal Article Brain Res · August 18, 1980 Kindling induces a decline of hippocampal muscarinic cholinergic receptors. To test the hypthesis that the decline was mediated by the agonist, acetylcholine, adult male Sprague--Dawley rats were lesioned in the medial septum prior to kindling. Despite the ... Full text Link to item Cite

Repeated seizures induce long-term increase in hippocampal benzodiazepine receptors.

Journal Article Proc Natl Acad Sci U S A · May 1980 Repeated seizures, whether induced by kindling or electroshock, caused a long-lasting (at least 24 hr) increase of [3H]diazepam binding in hippocampal membranes of Sprague-Dawley rats. Scatchard analyses demonstrated that increased numbers of binding sites ... Full text Link to item Cite

Muscarinic cholinergic regulation of epileptic spiking in kindling.

Journal Article Brain Res · December 7, 1979 Electroencephalographic monitoring of spontaneous interictal spiking (SIS) following kindling demonstrated that SIS occurs in both amygdalas and that it declines sharply during the days following kindling. Systemically administered muscarinic antagonists w ... Full text Link to item Cite

Spontaneous interictal spiking in the awake kindled rat.

Journal Article Electroencephalogr Clin Neurophysiol · November 1979 The spontaneous interictal spike (SIS) noted in EEG recordings is a signal of the abnormally excitable behavior of neurons in an epileptic focus. This study provides a detailed, quantitative, temporal and spatial profile of SIS in the amygdaloid kindled ra ... Full text Link to item Cite

The value of carotid endarterectomy in treating transient cerebral ischemia of the posterior circulation.

Journal Article Neurology · July 1977 The results of a retrospective study of patients undergoing carotid endarterectomy for hemispheric and/or nonhemispheric symptoms of transient ischemic attacks are presented. During an approximately 3-year period of follow-up observation, recurrent cerebra ... Full text Link to item Cite

Biochemical approaches to dementia.

Journal Article Contemp Neurol Ser · 1977 Link to item Cite

Receptor binding studies in kindling

Journal Article Neurology · January 1, 1977 Cite

Congenital ichthyosis with spastic paraplegia of adult onset.

Journal Article Arch Neurol · October 1975 Two siblings had what we believe to be a unique disorder manifested by stationary congenital ichthyosiform erythroderma coupled with a slowly progressive spastic weakness of adult onset. The disorder was presumably inherited as an autosomal recessive trait ... Full text Link to item Cite

Centronuclear myopathy: histochemistry and electron microscopy. Report of two cases.

Journal Article Arch Pathol · January 1975 In two new cases of centronuclear myopathy, histochemical findings included failure to differentiate fiber type with oxidative enzymes, the presence of core glycogenosis, and core acid phosphatase activity. Fluorescence microscopy demonstrated autofluoresc ... Link to item Cite