Scholars@Duke
Huaxin Sheng

Huaxin Sheng

Professor in Anesthesiology
Anesthesiology
sheng001@mc.duke.edu
Box 3094 Med Ctr, Durham, NC 27710
138 Sands Bldg, Durham, NC 27710

Selected Publications

Activation of Intestinal Mast Cells Contributes to Gut Damage After Cardiac Arrest in Mice.

Journal Article Shock · January 1, 2026 Sudden cardiac arrest (CA) is associated with high mortality and morbidity rates, largely due to detrimental effects of global ischemia on every organ. Notably, clinical evidence indicates that gastrointestinal tract damage is frequently observed in succes ... Full text Link to item Cite

Activation of ATF6 Signaling Confers Long-Term Beneficial Effects in Young and Aged Mice After Permanent Stroke.

Journal Article Transl Stroke Res · October 2025 Ischemic stroke disrupts protein homeostasis in brain cells, causes endoplasmic reticulum (ER) stress, and consequently activates the unfolded protein response (UPR). The primary function of UPR activation is to help cells restore ER function, thereby prom ... Full text Link to item Cite

SUMOylation Regulates Neutrophil Phagocytosis and Migration.

Journal Article Pharmaceuticals (Basel) · July 20, 2025 Introduction: Accumulating evidence indicates that neutrophils undergo reprogramming of their effector functions as they migrate from the bloodstream into an inflamed tissue. Here, we examined the role of the small ubiquitin-like modifier (SUMO) conjugatio ... Full text Link to item Cite

Deep-tissue high-sensitivity multimodal imaging and optogenetic manipulation enabled by biliverdin reductase knockout.

Journal Article Nat Commun · July 14, 2025 Performance of near-infrared probes and optogenetic tools derived from bacterial phytochromes is limited by availability of their biliverdin chromophore. To address this, we use a biliverdin reductase-A knock-out mouse model (Blvra-/-), which elevates endo ... Full text Link to item Cite

Glucocorticoid signaling mediates lymphopoiesis impairment after cardiac arrest in mice.

Journal Article J Cereb Blood Flow Metab · June 2025 Cardiac arrest (CA) is a life-threatening condition that requires immediate medical attention. Considerable advances in resuscitation have led to an increasing number of patients who survive the initial arrest event. However, among this growing patient pop ... Full text Link to item Cite

Treatment with Manganese Porphyrin, MnTnBuOE-2-PyP5+, Suppressed the Activation of Macrophages in a Mouse Intracerebral Hemorrhage.

Journal Article Pharmaceuticals (Basel) · April 8, 2025 Background: Manganese porphyrin, MnTnBuOE-2-PyP5+ (BMX-001), improves neurologic deficits in experimental ischemic stroke and has the potential to serve as an adjunct with thrombolysis or thrombectomy in stroke patients. In 10-30% of stroke patients follow ... Full text Link to item Cite

Ischemic stroke reduces bone perfusion and alters osteovascular structure.

Journal Article Bone Rep · March 2025 Stroke patients lose bone mass and experience fracture at an elevated rate. Although functional intraosseous vasculature is necessary for skeletal maintenance, the effect of stroke on osteovasculature is unknown. In this study we characterized changes to o ... Full text Link to item Cite

Early Autonomic Dysfunction in Traumatic Brain Injury: An Article Review on the Impact on Multiple Organ Dysfunction.

Journal Article J Clin Med · January 16, 2025 Background/Objectives: Traumatic brain injury (TBI) is a complex condition and a leading cause of injury-related disability and death, with significant impacts on patient outcomes. Extracranial organ involvement plays a critical role in the outcome of pati ... Full text Link to item Cite

Suppression of Paclitaxel-Induced Neuropathy and Ovarian Tumor Growth by Mn Porphyrin, MnTnBuOE-2-PyP5+ (BMX-001).

Journal Article Oxid Med Cell Longev · 2025 Numerous cellular and animal studies demonstrated the ability of redox-active Mn(III) N-alkyl- and N-alkoxyalkylpyridyporphyrins (MnPs) to protect normal tissue while suppressing tumor growth. The mechanism primarily involves the modulation of NF-кB and Nr ... Full text Link to item Cite

Advanced deep-tissue imaging and manipulation enabled by biliverdin reductase knockout.

Journal Article bioRxiv · October 18, 2024 We developed near-infrared (NIR) photoacoustic and fluorescence probes, as well as optogenetic tools from bacteriophytochromes, and enhanced their performance using biliverdin reductase-A knock-out model (Blvra-/-). Blvra-/- elevates endogenous heme-derive ... Full text Link to item Cite

Microglial heterogeneity in the ischemic stroke mouse brain of both sexes.

Journal Article Genome Med · August 2, 2024 BACKGROUND: Ischemic stroke elicits a complex and sustained immune response in the brain. Immunomodulatory treatments have long held promise for improving stroke outcomes, yet none have succeeded in the clinical setting. This lack of success is largely due ... Full text Link to item Cite

Multi-molecular hyperspectral PRM-SRS microscopy.

Journal Article Nat Commun · February 21, 2024 Lipids play crucial roles in many biological processes. Mapping spatial distributions and examining the metabolic dynamics of different lipid subtypes in cells and tissues are critical to better understanding their roles in aging and diseases. Commonly use ... Full text Link to item Cite

Data analysis protocol for early autonomic dysfunction characterization after severe traumatic brain injury.

Journal Article Front Neurol · 2024 BACKGROUND: Traumatic brain injury (TBI) disrupts normal brain tissue and functions, leading to high mortality and disability. Severe TBI (sTBI) causes prolonged cognitive, functional, and multi-organ dysfunction. Dysfunction of the autonomic nervous syste ... Full text Link to item Cite

Intracarotid Infusion of Redox-Active Manganese Porphyrin, MnTnBuOE-2-PyP5+, following Reperfusion Improves Long-Term, 28-Day Post-Stroke Outcomes in Rats.

Journal Article Antioxidants (Basel) · October 13, 2023 Endovascular mechanical thrombectomy, combined with a tissue plasminogen activator (t-PA), is efficacious as a standard care for qualifying ischemic stroke patients. However, > 50% of thrombectomy patients still have poor outcomes. Manganese porphyrins, co ... Full text Link to item Cite

Epinephrine-induced Effects on Cerebral Microcirculation and Oxygenation Dynamics Using Multimodal Monitoring and Functional Photoacoustic Microscopy.

Journal Article Anesthesiology · August 1, 2023 BACKGROUND: The administration of epinephrine after severe refractory hypotension, shock, or cardiac arrest restores systemic blood flow and major vessel perfusion but may worsen cerebral microvascular perfusion and oxygen delivery through vasoconstriction ... Full text Link to item Cite

SIRT1 Activation Promotes Long-Term Functional Recovery After Subarachnoid Hemorrhage in Rats.

Journal Article Neurocrit Care · June 2023 BACKGROUND: An increase in sirtuin 1 (SIRT1) reportedly attenuates early brain injury, delayed cerebral ischemia, and short-term neurologic deficits in rodent models of subarachnoid hemorrhage (SAH). This study investigates the effect of resveratrol, a SIR ... Full text Link to item Cite

A Modified Transcranial Middle Cerebral Artery Occlusion Model to Study Stroke Outcomes in Aged Mice.

Journal Article J Vis Exp · May 5, 2023 In experimental stroke research, middle cerebral artery occlusion (MCAO) with an intraluminal filament is widely used to model ischemic stroke in mice. The filament MCAO model typically exhibits a massive cerebral infarction in C57Bl/6 mice that sometimes ... Full text Link to item Cite

Mouse Cardiac Arrest Model for Brain Imaging and Brain Physiology Monitoring During Ischemia and Resuscitation.

Journal Article J Vis Exp · April 14, 2023 Most cardiac arrest (CA) survivors experience varying degrees of neurologic deficits. To understand the mechanisms that underpin CA-induced brain injury and, subsequently, develop effective treatments, experimental CA research is essential. To this end, a ... Full text Link to item Cite

A mast cell-thermoregulatory neuron circuit axis regulates hypothermia in anaphylaxis.

Journal Article Sci Immunol · March 17, 2023 IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing an e ... Full text Link to item Cite

Deep-tissue SWIR imaging using rationally designed small red-shifted near-infrared fluorescent protein.

Journal Article Nat Methods · January 2023 Applying rational design, we developed 17 kDa cyanobacteriochrome-based near-infrared (NIR-I) fluorescent protein, miRFP718nano. miRFP718nano efficiently binds endogenous biliverdin chromophore and brightly fluoresces in mammalian cells and tissues. miRFP7 ... Full text Open Access Link to item Cite

Myocardial Injury Caused by Chronic Alcohol Exposure-A Pilot Study Based on Proteomics.

Journal Article Molecules · July 3, 2022 Chronic alcohol exposure can cause myocardial degenerative diseases, manifested as cardiac insufficiency, arrhythmia, etc. These are defined as alcoholic cardiomyopathy (ACM). Alcohol-mediated myocardial injury has previously been studied through metabolom ... Full text Link to item Cite

Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats.

Journal Article Biology (Basel) · June 24, 2022 Introduction Cardiac arrest (CA) and resuscitation induces global cerebral ischemia and reperfusion, causing neurologic deficits or death. Manganese porphyrins, superoxide dismutase mimics, are reportedly able to effectively reduce ischemic injury in brain ... Full text Link to item Cite

Post-ischemia common carotid artery occlusion worsens memory loss, but not sensorimotor deficits, in long-term survived stroke mice.

Journal Article Brain Res Bull · June 1, 2022 Ischemic stroke in rodents is usually induced by intraluminal occlusion of the middle cerebral artery (MCA) via the external carotid artery (ECA) or the common carotid artery (CCA). The latter route requires permanent CCA occlusion after ischemia, and here ... Full text Open Access Link to item Cite

Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy.

Journal Article Light Sci Appl · May 17, 2022 High-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research. High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks, an ... Full text Open Access Link to item Cite

Single-cell transcriptomic analysis of the immune cell landscape in the aged mouse brain after ischemic stroke.

Journal Article J Neuroinflammation · April 7, 2022 BACKGROUND: Ischemic stroke is a medical emergency that primarily affects the elderly. A complex immune response in the post-stroke brain constitutes a key component of stroke pathophysiology. This study aimed to determine how stroke affects immune cell po ... Full text Open Access Link to item Cite

Endovascular middle cerebral artery embolic stroke model: a novel approach.

Journal Article J Neurointerv Surg · April 2022 A video (video 1) describing a novel murine endovascular embolic stroke model is presented. Traditional middle cerebral artery (MCA) occlusion models include a blind insertion of a monofilament string1 2 into the common or external carotid artery with the ... Full text Open Access Link to item Cite

Cervical Vagus Nerve Stimulation Improves Neurologic Outcome After Cardiac Arrest in Mice by Attenuating Oxidative Stress and Excessive Autophagy.

Journal Article Neuromodulation · April 2022 BACKGROUND: Cerebral ischemia and reperfusion (I/R) induces oxidative stress and activates autophagy, leading to brain injury and neurologic deficits. Cervical vagus nerve stimulation (VNS) increases cerebral blood flow (CBF). In this study, we investigate ... Full text Open Access Link to item Cite

Effects of Long-Term Vagus Nerve Electrical Stimulation Therapy on Acute Cerebral Infarction and Neurological Function Recovery in Post MCAO Mice.

Journal Article Oxidative medicine and cellular longevity · January 2022 BackgroundVagus nerve stimulation therapy is proven to produce neuroprotective effects against central nervous system diseases and reduce neurological injury, having a positive effect on the recovery of neurological functions in mouse model of str ... Full text Open Access Cite

Beneficial effects of neuronal ATF6 activation in permanent ischemic stroke.

Journal Article Front Cell Neurosci · 2022 Objective: Brain ischemia leads to the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) lumen and consequently, ER stress. To help cells restore ER function, a series of adaptive stress response pathways, collectively termed th ... Full text Link to item Cite

Activation of the XBP1s/O-GlcNAcylation Pathway Improves Functional Outcome After Cardiac Arrest and Resuscitation in Young and Aged Mice.

Journal Article Shock · November 1, 2021 After cardiac arrest (CA) and resuscitation, the unfolded protein response (UPR) is activated in various organs including the brain. However, the role of the UPR in CA outcome remains largely unknown. One UPR branch involves spliced X-box-binding protein-1 ... Full text Open Access Link to item Cite

Photoacoustic imaging of in vivo hemodynamic responses to sodium nitroprusside.

Journal Article J Biophotonics · July 2021 The in vivo hemodynamic impact of sodium nitroprusside (SNP), a widely used antihypertensive agent, has not been well studied. Here, we applied functional optical-resolution photoacoustic microscopy (OR-PAM) to study the hemodynamic responses to SNP in mic ... Full text Open Access Link to item Cite

Activation of the ATF6 (Activating Transcription Factor 6) Signaling Pathway in Neurons Improves Outcome After Cardiac Arrest in Mice.

Journal Article J Am Heart Assoc · June 15, 2021 Background Ischemia/reperfusion injury impairs proteostasis, and triggers adaptive cellular responses, such as the unfolded protein response (UPR), which functions to restore endoplasmic reticulum homeostasis. After cardiac arrest (CA) and resuscitation, t ... Full text Open Access Link to item Cite

Development and Evaluation of a Novel Mouse Model of Asphyxial Cardiac Arrest Revealed Severely Impaired Lymphopoiesis After Resuscitation.

Journal Article J Am Heart Assoc · June 2021 Background Animal disease models represent the cornerstone in basic cardiac arrest (CA) research. However, current experimental models of CA and resuscitation in mice are limited. In this study, we aimed to develop a mouse model of asphyxial CA followed by ... Full text Open Access Link to item Cite

Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.

Journal Article J Cereb Blood Flow Metab · May 2021 In patients who are successfully resuscitated after initial cardiac arrest (CA), mortality and morbidity rates are high, due to ischemia/reperfusion injury to the whole body including the nervous and immune systems. How the interactions between these two c ... Full text Open Access Link to item Cite

Increasing O-GlcNAcylation is neuroprotective in young and aged brains after ischemic stroke.

Journal Article Exp Neurol · May 2021 Spliced X-box binding protein-1 (XBP1s) together with the hexosamine biosynthetic pathway (HBP) and O-GlcNAcylation forms the XBP1s/HBP/O-GlcNAc axis. Our previous studies have provided evidence that activation of this axis is neuroprotective after ischemi ... Full text Open Access Link to item Cite

H2O2-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways.

Journal Article Oxid Med Cell Longev · 2021 Mn(III) ortho-N-alkyl- and N-alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO-, H2O2, H2S, CO3 •-, ascorbate, and GSH). Moreo ... Full text Open Access Link to item Cite

Small ubiquitin-like modifier 2 (SUMO2) is critical for memory processes in mice.

Journal Article FASEB J · November 2020 Small ubiquitin-like modifier (SUMO1-3) conjugation (SUMOylation), a posttranslational modification, modulates almost all major cellular processes. Mounting evidence indicates that SUMOylation plays a crucial role in maintaining and regulating neural funct ... Full text Open Access Link to item Cite

MnTnBuOE-2-PyP5+ Ascorbate in the Treatment of Ovarian Cancer

Conference Free Radical Biology and Medicine · November 2020 Full text Cite

MCC950, a selective NLPR3 inflammasome inhibitor, improves neurologic function and survival after cardiac arrest and resuscitation.

Journal Article J Neuroinflammation · August 31, 2020 BACKGROUND: Cardiac arrest (CA) is associated with high morbidity and mortality, even after spontaneous circulation is re-established. This dire situation is partly due to post-CA syndrome for which no specific and effective intervention is available. One ... Full text Open Access Link to item Cite

Long-term chemogenetic activation of M1 glutamatergic neurons attenuates the behavioral and cognitive deficits caused by intracerebral hemorrhage.

Journal Article Biochem Biophys Res Commun · June 18, 2020 Acute spontaneous intracerebral hemorrhage (ICH) is a life-threatening disease. It is often accompanied by severe neurological sequelae largely caused by the loss of integrity of the neural circuits. However, these neurological sequelae have few strong med ... Full text Open Access Link to item Cite

Fe Porphyrin-Based SOD Mimic and Redox-Active Compound, (OH)FeTnHex-2-PyP4+, in a Rodent Ischemic Stroke (MCAO) Model: Efficacy and Pharmacokinetics as Compared to Its Mn Analogue, (H2O)MnTnHex-2-PyP5+.

Journal Article Antioxidants (Basel) · June 1, 2020 Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, (H2O)MnTnHex-2-PyP5+ (MnHex) carrying long hexyl chains, is a lipophilic mimic of superoxide dismutase (SOD) and a redox-active drug candidate. MnHex crosses the blood-brain barrier, and improved ne ... Full text Open Access Link to item Cite

PERK (Protein Kinase RNA-Like ER Kinase) Branch of the Unfolded Protein Response Confers Neuroprotection in Ischemic Stroke by Suppressing Protein Synthesis.

Journal Article Stroke · May 2020 Background and Purpose- Ischemic stroke impairs endoplasmic reticulum (ER) function, causes ER stress, and activates the unfolded protein response. The unfolded protein response consists of 3 branches controlled by ER stress sensor proteins, which include ... Full text Open Access Link to item Cite

Chemogenetics-mediated acute inhibition of excitatory neuronal activity improves stroke outcome.

Journal Article Exp Neurol · April 2020 BACKGROUND AND PURPOSE: Ischemic stroke significantly perturbs neuronal homeostasis leading to a cascade of pathologic events causing brain damage. In this study, we assessed acute stroke outcome after chemogenetic inhibition of forebrain excitatory neuron ... Full text Open Access Link to item Cite

Stroke Prevents Exercise-Induced Gains in Bone Microstructure But Not Composition in Mice.

Journal Article J Biomech Eng · December 1, 2019 Ischemic stroke induces rapid loss in bone mineral density that is up to 13 times greater than during normal aging, leading to a markedly increased risk of fracture. Little is known about skeletal changes following stroke beyond density loss. In this study ... Full text Open Access Link to item Cite

Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome.

Journal Article Crit Care Med · August 2019 OBJECTIVES: We tested the hypothesis that prolonged inhalation of 70% argon for 24 hours after in vivo permanent or temporary stroke provides neuroprotection and improves neurologic outcome and overall recovery after 7 days. DESIGN: Controlled, randomized, ... Full text Open Access Link to item Cite

High-speed widefield photoacoustic microscopy of small-animal hemodynamics.

Journal Article Biomed Opt Express · October 1, 2018 Optical-resolution photoacoustic microscopy (OR-PAM) has become a popular tool in small-animal hemodynamic studies. However, previous OR-PAM techniques variously lacked a high imaging speed and/or a large field of view, impeding the study of highly dynamic ... Full text Open Access Link to item Cite

Aging Is Associated With Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice.

Journal Article J Am Heart Assoc · September 4, 2018 Background The mechanisms underlying worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation are not well understood. Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , ... Full text Open Access Link to item Cite

Novel Treatment of Cryptococcal Meningitis via Neurapheresis Therapy.

Journal Article J Infect Dis · August 24, 2018 Cryptococcal meningitis (CM) has emerged as the most common life-threatening fungal meningitis worldwide. Current management involves a sequential, longitudinal regimen of antifungals; despite a significant improvement in survival compared with uniform mor ... Full text Open Access Link to item Cite

Ubc9 overexpression and SUMO1 deficiency blunt inflammation after intestinal ischemia/reperfusion.

Journal Article Lab Invest · June 2018 The intestinal epithelium constitutes a crucial defense to the potentially life-threatening effects of gut microbiota. However, due to a complex underlying vasculature, hypoperfusion and resultant tissue ischemia pose a particular risk to function and inte ... Full text Open Access Link to item Cite

Novel Modification of Potassium Chloride Induced Cardiac Arrest Model for Aged Mice.

Journal Article Aging Dis · February 2018 Experimental cardiac arrest (CA) in aging research is infrequently studied in part due to the limitation of animal models. We aimed to develop an easily performed mouse CA model to meet this need. A standard mouse KCl-induced CA model using chest compressi ... Full text Open Access Link to item Cite

XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.

Journal Article Stroke · June 2017 BACKGROUND AND PURPOSE: Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke. To restore endoplasmic reticulum function impaired by stress, the unfolded prote ... Full text Open Access Link to item Cite

Xenon as a therapy in experimental intracerebral hemorrhage

Conference JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM · April 1, 2017 Link to item Cite

Activation of the ATF6 branch of the unfolded protein response in neurons improves stroke outcome.

Journal Article J Cereb Blood Flow Metab · March 2017 Impaired function of the endoplasmic reticulum (ER stress) is a hallmark of many human diseases including stroke. To restore ER function in stressed cells, the unfolded protein response (UPR) is induced, which activates 3 ER stress sensor proteins includin ... Full text Open Access Link to item Cite

Neuron-specific SUMO knockdown suppresses global gene expression response and worsens functional outcome after transient forebrain ischemia in mice.

Journal Article Neuroscience · February 20, 2017 Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) plays key roles in neurologic function in health and disease. Neuronal SUMOylation is essential for emotionality and cognition, and this pathway is dramatically activated in post-ischemic neuro ... Full text Open Access Link to item Cite

Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage.

Journal Article Cell Physiol Biochem · 2017 BACKGROUND/AIMS: Intracerebral hemorrhage (ICH) occurs in hypertensive patients and results in high rates of mortality and disability. This study determined whether bone marrow mesenchymal stem cell (BMSC) transplantation affects axonal regeneration and ex ... Full text Open Access Link to item Cite

Video training and certification program improves reliability of postischemic neurologic deficit measurement in the rat.

Journal Article J Cereb Blood Flow Metab · December 2016 Scoring systems are used to measure behavioral deficits in stroke research. Video-assisted training is used to standardize stroke-related neurologic deficit scoring in humans. We hypothesized that a video-assisted training and certification program can imp ... Full text Open Access Link to item Cite

Redox-Active Therapeutics

Book · October 13, 2016 This essential volume comprehensively discusses redox-active therapeutics, focusing particularly on their molecular design, mechanistic, pharmacological and medicinal aspects. ... Open Access Cite

Long-Term Cognitive Deficits After Subarachnoid Hemorrhage in Rats.

Journal Article Neurocrit Care · October 2016 BACKGROUND: Cognitive dysfunction can be a long-term complication following subarachnoid hemorrhage (SAH). Preclinical models have been variously characterized to emulate this disorder. This study was designed to directly compare long-term cognitive defici ... Full text Open Access Link to item Cite

Anesthesia in Experimental Stroke Research.

Journal Article Transl Stroke Res · October 2016 Anesthetics have enabled major advances in development of experimental models of human stroke. Yet, their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have species-, drug-, a ... Full text Open Access Link to item Cite

Targeting the SUMO pathway for neuroprotection in brain ischaemia.

Journal Article Stroke and vascular neurology · September 2016 Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) is a post-translational protein modification that modulates almost all major cellular processes, and has been implicated in many human diseases. A growing body of evidence from in vitro and in ... Full text Open Access Cite

Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume.

Journal Article J Clin Invest · August 1, 2016 Risk for ischemic stroke has a strong genetic basis, but heritable factors also contribute to the extent of damage after a stroke has occurred. We previously identified a locus on distal mouse chromosome 7 that contributes over 50% of the variation in post ... Full text Open Access Link to item Cite

Novel approaches to neuroprotection

Conference JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM · June 1, 2016 Link to item Cite

CHARACTERIZATION OF A MODIFIED LONG TERM SURVIVAL MOUSE MODEL OF CEREBRAL ISCHEMIA

Conference JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM · June 1, 2016 Link to item Cite

O-linked β-N-acetylglucosamine modification of proteins is activated in post-ischemic brains of young but not aged mice: Implications for impaired functional recovery from ischemic stress.

Journal Article J Cereb Blood Flow Metab · February 2016 To evaluate the effect of age on the response of brains to an ischemic challenge, we subjected young and aged mice to transient forebrain ischemia, and analyzed the heat shock response and unfolded protein response, ubiquitin conjugation and SUMO conjugati ... Full text Open Access Link to item Cite

Progesterone Improves Neurobehavioral Outcome in Models of Intracerebral Hemorrhage.

Conference Neuroendocrinology · 2016 In models of acute brain injury, progesterone improves recovery through several mechanisms including modulation of neuroinflammation. Secondary injury from neuroinflammation is a potential therapeutic target after intracerebral hemorrhage (ICH). For potent ... Full text Link to item Cite

Sex-Specific Effects of Progesterone on Early Outcome of Intracerebral Hemorrhage.

Journal Article Neuroendocrinology · 2016 BACKGROUND: Preclinical evidence suggests that progesterone improves recovery after intracerebral hemorrhage (ICH); however, gonadal hormones have sex-specific effects. Therefore, an experimental model of ICH was used to assess recovery after progesterone ... Full text Open Access Link to item Cite

Novel Manganese-Porphyrin Superoxide Dismutase-Mimetic Widens the Therapeutic Margin in a Preclinical Head and Neck Cancer Model.

Journal Article Int J Radiat Oncol Biol Phys · November 15, 2015 PURPOSE: To test the effects of a novel Mn porphyrin oxidative stress modifier, Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE), for its radioprotective and radiosensitizing properties in normal tissue versus tumor, respectively. ME ... Full text Open Access Link to item Cite

CB1 cannabinoid receptor agonist inhibits matrix metalloproteinase activity in spinal cord injury: A possible mechanism of improved recovery.

Journal Article Neurosci Lett · June 15, 2015 Increased matrix metalloproteinase (MMP) activity contributes to glial scar formation that inhibits the repair path after spinal cord injury (SCI). We examined whether treatment with N-​(2-​chloroethyl)-​5Z,​8Z,​11Z,​14Z-​eicosatetraenamide (ACEA), a selec ... Full text Open Access Link to item Cite

Sustained functional improvement by hepatocyte growth factor-like small molecule BB3 after focal cerebral ischemia in rats and mice.

Journal Article J Cereb Blood Flow Metab · June 2015 Hepatocyte growth factor (HGF), efficacious in preclinical models of acute central nervous system injury, is burdened by administration of full-length proteins. A multiinstitutional consortium investigated the efficacy of BB3, a small molecule with HGF-lik ... Full text Open Access Link to item Cite

A blinded randomized assessment of laser Doppler flowmetry efficacy in standardizing outcome from intraluminal filament MCAO in the rat.

Journal Article J Neurosci Methods · February 15, 2015 BACKGROUND: Laser Doppler flowmetry (LDF) is widely used for estimating cerebral blood flow changes during intraluminal middle cerebral artery occlusion (MCAO). No investigation has systematically examined LDF efficacy in standardizing outcome. We examined ... Full text Open Access Link to item Cite

Intrastriatal injection of autologous blood or clostridial collagenase as murine models of intracerebral hemorrhage.

Journal Article J Vis Exp · July 3, 2014 Intracerebral hemorrhage (ICH) is a common form of cerebrovascular disease and is associated with significant morbidity and mortality. Lack of effective treatment and failure of large clinical trials aimed at hemostasis and clot removal demonstrate the nee ... Full text Open Access Link to item Cite

ApoE mimetic ameliorates motor deficit and tissue damage in rat spinal cord injury.

Journal Article J Neurosci Res · July 2014 Apolipoprotein E (apoE), a plasma protein responsible for transporting lipid and cholesterol, modulates responses of the central nervous system to injury. Small peptides derived from the receptor-binding region of apoE can simulate some important bioactivi ... Full text Open Access Link to item Cite

Neuron-specific Sumo1-3 knockdown in mice impairs episodic and fear memories.

Journal Article J Psychiatry Neurosci · July 2014 BACKGROUND: Growing evidence suggests that small ubiquitin-like modifier (SUMO) conjugation plays a key role in brain plasticity by modulating activity-dependent synaptic transmission. However, these observations are based largely on cell culture experimen ... Full text Open Access Link to item Cite

Metalloporphyrins as therapeutic catalytic oxidoreductants in central nervous system disorders.

Journal Article Antioxid Redox Signal · May 20, 2014 SIGNIFICANCE: Metalloporphyrins, characterized by a redox-active transitional metal (Mn or Fe) coordinated to a cyclic porphyrin core ligand, mitigate oxidative/nitrosative stress in biological systems. Side-chain substitutions tune redox properties of met ... Full text Open Access Link to item Cite

Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in novel small ubiquitin-like modifier transgenic mice: putative protective proteins/pathways.

Journal Article Stroke · April 2014 BACKGROUND AND PURPOSE: Small ubiquitin-like modifier (SUMO) conjugation is a post-translational modification associated with many human diseases. Characterization of the SUMO-modified proteome is pivotal to define the mechanistic link between SUMO conjuga ... Full text Open Access Link to item Cite

Characterization of the ubiquitin-modified proteome regulated by transient forebrain ischemia.

Journal Article J Cereb Blood Flow Metab · March 2014 Ubiquitylation is a posttranslational protein modification that modulates various cellular processes of key significance, including protein degradation and DNA damage repair. In animals subjected to transient cerebral ischemia, ubiquitin-conjugated protein ... Full text Open Access Link to item Cite

Differential coordination demands in Fe versus Mn water-soluble cationic metalloporphyrins translate into remarkably different aqueous redox chemistry and biology.

Journal Article Inorg Chem · May 20, 2013 The different biological behavior of cationic Fe and Mn pyridylporphyrins in Escherichia coli and mouse studies prompted us to revisit and compare their chemistry. For that purpose, the series of ortho and meta isomers of Fe(III) meso-tetrakis-N-alkylpyrid ... Full text Open Access Link to item Cite

Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4.

Journal Article Nature · May 16, 2013 Postnatal/adult neural stem cells (NSCs) within the rodent subventricular zone (SVZ; also called subependymal zone) generate doublecortin (Dcx)(+) neuroblasts that migrate and integrate into olfactory bulb circuitry. Continuous production of neuroblasts is ... Full text Open Access Link to item Cite

Comprehensive pharmacokinetic studies and oral bioavailability of two Mn porphyrin-based SOD mimics, MnTE-2-PyP5+ and MnTnHex-2-PyP5+.

Journal Article Free Radic Biol Med · May 2013 The cationic, ortho Mn(III) N-alkylpyridylporphyrins (alkyl=ethyl, E, and n-hexyl, nHex) MnTE-2-PyP(5+) (AEOL10113, FBC-007) and MnTnHex-2-PyP(5+) have proven efficacious in numerous in vivo animal models of diseases having oxidative stress in common. The ... Full text Open Access Link to item Cite

Lack of evidence for a remote effect of renal ischemia/reperfusion acute kidney injury on outcome from temporary focal cerebral ischemia in the rat.

Journal Article J Cardiothorac Vasc Anesth · February 2013 OBJECTIVE: Acute kidney injury (AKI) and ischemic stroke may occur in the same cardiac surgical patient. It is not known if an interaction exists between these organ injuries. Isolated renal ischemia/reperfusion is associated with dysfunction in remote, ot ... Full text Open Access Link to item Cite

Transient ischemia induces massive nuclear accumulation of SUMO2/3-conjugated proteins in spinal cord neurons.

Journal Article Spinal Cord · February 2013 OBJECTIVES: The objective of this study is to determine whether transient spinal cord ischemia activates small ubiquitin-like modifier (SUMO1-3) conjugation, a post-translational protein modification that protects neurons from ischemia-like conditions. MET ... Full text Open Access Link to item Cite

Design, mechanism of action, bioavailability and therapeutic effects of mn porphyrin-based redox modulators.

Journal Article Med Princ Pract · 2013 Based on aqueous redox chemistry and simple in vivo models of oxidative stress, Escherichia coli and Saccharomyces cerevisiae, the cationic Mn(III) N-substituted pyridylporphyrins (MnPs) have been identified as the most potent cellular redox modulators wit ... Full text Open Access Link to item Cite

Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4

Journal Article Nature · 2013 Postnatal/adult neural stem cells (NSCs) within the rodent subventricular zone (SVZ; also called subependymal zone) generate doublecortin (Dcx) + neuroblasts that migrate and integrate into olfactory bulb circuitry. Continuous production of neuroblasts is ... Full text Open Access Cite

Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage.

Journal Article Anesthesiology · December 2012 BACKGROUND: Xenon has been proven to be neuroprotective in experimental brain injury. The authors hypothesized that xenon would improve outcome from focal cerebral ischemia with a delayed treatment onset and prolonged recovery interval. METHODS: Rats were ... Full text Open Access Link to item Cite

A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity.

Journal Article Free Radic Biol Med · May 1, 2012 The Mn porphyrins of k(cat)(O(2)(.-)) as high as that of a superoxide dismutase enzyme and of optimized lipophilicity have already been synthesized. Their exceptional in vivo potency is at least in part due to their ability to mimic the site and location o ... Full text Open Access Link to item Cite

Analysis of oxygen/glucose-deprivation-induced changes in SUMO3 conjugation using SILAC-based quantitative proteomics.

Journal Article J Proteome Res · February 3, 2012 Transient cerebral ischemia dramatically activates small ubiquitin-like modifier (SUMO2/3) conjugation. In cells exposed to 6 h of transient oxygen/glucose deprivation (OGD), a model of ischemia, SUMOylation increases profoundly between 0 and 30 min follow ... Full text Open Access Link to item Cite

Neuroprotective efficacy from a lipophilic redox-modulating Mn(III) N-Hexylpyridylporphyrin, MnTnHex-2-PyP: rodent models of ischemic stroke and subarachnoid hemorrhage.

Journal Article J Pharmacol Exp Ther · September 2011 Intracerebroventricular treatment with redox-regulating Mn(III) N-hexylpyridylporphyrin (MnPorphyrin) is remarkably efficacious in experimental central nervous system (CNS) injury. Clinical development has been arrested because of poor blood-brain barrier ... Full text Open Access Link to item Cite

The effect of blood pressure on cerebral outcome in a rat model of cerebral air embolism during cardiopulmonary bypass.

Journal Article J Thorac Cardiovasc Surg · August 2011 OBJECTIVE: Higher mean arterial pressure during cardiopulmonary bypass may improve cerebral outcome associated with cerebral air embolism by increasing emboli clearance and collateral flow to salvage the ischemic penumbra. However, this may come at the exp ... Full text Open Access Link to item Cite

Methoxy-derivatization of alkyl chains increases the in vivo efficacy of cationic Mn porphyrins. Synthesis, characterization, SOD-like activity, and SOD-deficient E. coli study of meta Mn(III) N-methoxyalkylpyridylporphyrins.

Journal Article Dalton Trans · April 28, 2011 Cationic Mn(III) N-alkylpyridylporphyrins (MnPs) are potent SOD mimics and peroxynitrite scavengers and diminish oxidative stress in a variety of animal models of central nervous system (CNS) injuries, cancer, radiation, diabetes, etc. Recently, properties ... Full text Open Access Link to item Cite

Pharmacologically augmented S-nitrosylated hemoglobin improves recovery from murine subarachnoid hemorrhage.

Journal Article Stroke · February 2011 Featured Publication BACKGROUND AND PURPOSE: S-nitrosylated hemoglobin (S-nitrosohemoglobin) has been implicated in the delivery of O(2) to tissues through the regulation of microvascular blood flow. This study tested the hypothesis that enhancement of S-nitrosylated hemoglobi ... Full text Open Access Link to item Cite

Aprotinin improves functional outcome but not cerebral infarct size in an experimental model of stroke during cardiopulmonary bypass.

Journal Article Anesth Analg · July 2010 BACKGROUND: Aprotinin, a nonspecific serine protease inhibitor, has been used to decrease bleeding and reduce the systemic inflammatory response after cardiopulmonary bypass (CPB). Studies have variably linked aprotinin administration with both improved as ... Full text Open Access Link to item Cite

Development of a simplified spinal cord ischemia model in mice.

Journal Article J Neurosci Methods · June 15, 2010 Featured Publication Use of genetically manipulated mice facilitates understanding pathological mechanisms in many diseases and contributes to therapy development. However, there is no practical and clinically relevant mouse model available for spinal cord ischemia. This repor ... Full text Open Access Link to item Cite

Simvastatin treatment duration and cognitive preservation in experimental subarachnoid hemorrhage.

Journal Article J Neurosurg Anesthesiol · October 2009 Cognitive dysfunction, a significant complication after subarachnoid hemorrhage (SAH), affects up to 60% of survivors. We hypothesized that oral simvastatin would improve vestibulomotor function and reduce cognitive dysfunction after experimental SAH in th ... Full text Link to item Cite

Long-term neuroprotection from a potent redox-modulating metalloporphyrin in the rat.

Journal Article Free Radic Biol Med · October 1, 2009 Featured Publication Sustained oxidative stress is a known sequel to focal cerebral ischemia. This study examined the effects of treatment with a single dose or sustained infusion of the redox-modulating MnPorphyrin Mn(III)TDE-2-ImP(5+) on outcome from middle cerebral artery o ... Full text Link to item Cite

TRANSIENT CEREBRAL ISCHEMIA AND PROTEIN SUMOYLATION

Journal Article JOURNAL OF NEUROCHEMISTRY · March 1, 2009 Link to item Cite

Long-term cognitive dysfunction following experimental subarachnoid hemorrhage: new perspectives.

Journal Article Exp Neurol · October 2008 Cognitive dysfunction is increasingly recognized as a significant long-term complication following subarachnoid hemorrhage (SAH), affecting up to 60% of survivors. We proposed to determine the incidence and explore potential mechanisms of cognitive dysfunc ... Full text Link to item Cite

Cerebral ischemia/stroke and small ubiquitin-like modifier (SUMO) conjugation--a new target for therapeutic intervention?

Journal Article J Neurochem · August 2008 Transient cerebral ischemia/stroke activates various post-translational protein modifications such as phosphorylation and ubiquitin conjugation that are believed to play a major role in the pathological process triggered by an interruption of blood supply ... Full text Link to item Cite

Transient focal cerebral ischemia induces a dramatic activation of small ubiquitin-like modifier conjugation.

Journal Article J Cereb Blood Flow Metab · May 2008 This study was designed to investigate whether small ubiquitin-like modifier (SUMO) conjugation is activated after focal cerebral ischemia. Transient ischemia induced a dramatic increase in SUMO2/3 protein conjugates. The most pronounced changes were found ... Full text Link to item Cite

Transient global cerebral ischemia induces a massive increase in protein sumoylation.

Journal Article J Cereb Blood Flow Metab · February 2008 A new group of proteins, small ubiquitin-like modifier (SUMO) proteins, has recently been identified and protein sumoylation has been shown to play a major role in various signal transduction pathways. Here, we report that transient global cerebral ischemi ... Full text Link to item Cite

Superparamagnetic iron oxide labeling and transplantation of adipose-derived stem cells in middle cerebral artery occlusion-injured mice.

Journal Article AJR Am J Roentgenol · April 2007 OBJECTIVE: Adipose-derived stem cells are an alternative stem cell source for CNS therapies. The goals of the current study were to label adipose-derived stem cells with superparamagnetic iron oxide (SPIO) particles, to use MRI to guide the transplantation ... Full text Link to item Cite

Isoflurane provides long-term protection against focal cerebral ischemia in the rat.

Journal Article Anesthesiology · January 2007 BACKGROUND: Long-term neuroprotection by isoflurane has been questioned. The authors examined factors in experimental models potentially critical to definition of enduring isoflurane neuroprotection. METHODS: Rats were prepared for temporary middle cerebra ... Full text Link to item Cite

Selective gamma-aminobutyric acid type A receptor antagonism reverses isoflurane ischemic neuroprotection.

Journal Article Anesthesiology · July 2006 BACKGROUND: Isoflurane provides protection against severe forebrain ischemia in the rat. The authors hypothesized that this is attributable to interaction with the gamma-aminobutyric acid type A (GABAA) receptor resulting in altered time to onset of ischem ... Full text Link to item Cite

A comparison of hyperbaric oxygen versus hypoxic cerebral preconditioning in neonatal rats.

Journal Article Brain Res · February 23, 2006 The potency of hyperbaric preconditioning (HBO-PC) is uncertain compared to well-validated ischemic or hypoxic models and no studies have directly compared HBO-PC to hypoxic preconditioning (HPC). We subjected rat pups to unilateral carotid cauterization f ... Full text Link to item Cite

Effects of a manganese (III) porphyrin catalytic antioxidant in a mouse closed head injury model.

Journal Article Eur J Pharmacol · February 15, 2006 Closed head injury induces cerebral oxidative stress. The efficacy of a Mn (III) porphyrin catalytic antioxidant was assessed in a mouse closed head injury model. Mice were subjected to closed head injury and treated 15 min later with an i.v. bolus of vehi ... Full text Link to item Cite

Isoflurane provides sustained neuroprotection in rats subjected to focal ischemia

Journal Article Journal of Neurosurgical Anesthesiology · January 1, 2006 Abstracts published in the Journal of Neurosurgical Anesthesiology have been reviewed by the organizations or JNA Affiliate Societies at whose meetings the abstracts have been accepted for presentation. These abstracts have not undergone review by the Edit ... Full text Cite

A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage.

Journal Article Neurocrit Care · 2006 INTRODUCTION: Recent clinical observations demonstrate that the APOE4 genotype increases the development of delayed ischemic deficit and worsens prognosis following aneurysmal subarachnoid hemorrhage (SAH). In the current study, we use targeted replacement ... Full text Link to item Cite

Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage.

Journal Article Neurocrit Care · 2006 OBJECTIVES: Prophylactic treatment with antiepileptic drugs is common practice following subarachnoid hemorrhage (SAH) and traumatic brain injury. However, commonly used antiepileptic drugs have multiple drug interactions, require frequent monitoring of se ... Full text Link to item Cite

Intraischemic nitrous oxide alters neither neurologic nor histologic outcome: a comparison with dizocilpine.

Journal Article Anesth Analg · September 2004 N-Methyl-D-aspartate receptor antagonism contributes to the anesthetic action of nitrous oxide (N(2)O). We examined the effects of the N-methyl-D-aspartate antagonists N(2)O and dizocilpine on outcome from filament occlusion of the middle cerebral artery ( ... Full text Link to item Cite

Mouse spinal cord compression injury is ameliorated by intrathecal cationic manganese(III) porphyrin catalytic antioxidant therapy.

Journal Article Neurosci Lett · August 12, 2004 This study evaluated the effects of the cationic manganese(III) tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin catalytic antioxidant Mn(III)TDE-2-ImP5+ (AEOL 10150) on outcome from spinal cord compression (SCC) in the mouse. C57BL/6J mice were subjected t ... Full text Link to item Cite

Oxidants, antioxidants and the ischemic brain.

Journal Article J Exp Biol · August 2004 Despite numerous defenses, the brain is vulnerable to oxidative stress resulting from ischemia/reperfusion. Excitotoxic stimulation of superoxide and nitric oxide production leads to formation of highly reactive products, including peroxynitrite and hydrox ... Full text Link to item Cite

Effects of isoflurane versus fentanyl-nitrous oxide anesthesia on long-term outcome from severe forebrain ischemia in the rat.

Journal Article Anesthesiology · May 2004 BACKGROUND: This study examined long-term outcome from severe forebrain ischemia in the rat, as a function of anesthetic given during the ischemic injury. METHODS: Rats were subjected to 10 min of near-complete forebrain ischemia while anesthetized with ei ... Full text Link to item Cite

A no-laminectomy spinal cord compression injury model in mice.

Journal Article J Neurotrauma · May 2004 The purpose of this study was to develop a minimally invasive recovery model of spinal cord injury in the C57Bl/6J mouse. Without laminectomy, the epidural space was exposed by disruption of the T10-T11 interspinous ligament. Perpendicular to the rostral-c ... Full text Link to item Cite

Severe hypotension is not essential for isoflurane neuroprotection against forebrain ischemia in mice.

Journal Article Anesthesiology · November 2003 BACKGROUND: Volatile anesthetics provide protection in experimental models of global cerebral ischemia. To date, all models evaluated have included profound systemic arterial hypotension as a component of the ischemic insult. This study was designed to det ... Full text Link to item Cite

Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage.

Journal Article Stroke · February 2003 BACKGROUND AND PURPOSE: During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal ... Link to item Cite

Hemodynamic effects of metalloporphyrin catalytic antioxidants: structure-activity relationships and species specificity.

Journal Article Free Radic Biol Med · December 15, 2002 Superoxide plays a role in blood pressure regulation in certain vascular diseases, however, its involvement in regulating basal blood pressure is uncertain. Vascular superoxide concentrations are limited by extracellular superoxide dismutase (EC-SOD), whic ... Full text Link to item Cite

Catalytic Antioxidants as Novel Pharmacologic Approaches to Treatment of Ischemic Brain Injury.

Journal Article Drug News Perspect · December 2002 Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are increased following acute brain ischemia. These species have been associated with secondary injury that amplifies the magnitude of final neuronal damage. Work with both biochemical analy ... Full text Link to item Cite

Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage.

Journal Article Stroke · December 2002 BACKGROUND AND PURPOSE: Endothelial nitric oxide synthase (eNOS) activity is decreased after subarachnoid hemorrhage (SAH). Simvastatin increases eNOS activity. We hypothesized that simvastatin would increase eNOS protein and ameliorate SAH-induced cerebra ... Full text Link to item Cite

A catalytic antioxidant (AEOL 10150) attenuates expression of inflammatory genes in stroke.

Journal Article Free Radic Biol Med · October 15, 2002 Oxidative stress is a major source of injury from cerebral ischemia and reperfusion. We hypothesized that a catalytic antioxidant AEOL 10150 [manganese (III) meso-tetrakis (di-N-ethylimidazole) porphyrin] would attenuate changes in brain gene expression in ... Full text Link to item Cite

Effects of metalloporphyrin catalytic antioxidants in experimental brain ischemia.

Journal Article Free Radic Biol Med · October 1, 2002 Featured Publication Reactive oxygen species play a role in the response of brain to ischemia. The effects of metalloporphyrin catalytic antioxidants (AEOL 10113 and AEOL 10150) were examined after murine middle cerebral artery occlusion (MCAO). Ninety minutes after reperfusio ... Full text Link to item Cite

Attenuation of cerebral vasospasm after subarachnoid hemorrhage in mice overexpressing extracellular superoxide dismutase.

Journal Article Stroke · September 2002 BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) increases production of vascular extracellular superoxide anion (*O2-). We examined whether overexpression of murine extracellular superoxide dismutase (EC-SOD) alters SAH-induced cerebral vasospasm, ox ... Full text Link to item Cite

Mouse model of subarachnoid hemorrhage associated cerebral vasospasm: methodological analysis.

Journal Article Neurol Res · July 2002 The transgenic mouse has been used to study subarachnoid hemorrhage (SAH) induced delayed cerebral vasospasm (DCV). Methodological parameters have not been analyzed to validate this model and associated neurological deficits have not been described. We int ... Full text Link to item Cite

Pharmacological correction of hypothermic P(50) shift does not alter outcome from focal cerebral ischemia in rats.

Journal Article Am J Physiol Heart Circ Physiol · May 2002 Hypothermia decreases the arterial PO(2) at which hemoglobin is 50% saturated (P(50)), increasing hemoglobin O(2)-binding affinity. We used RSR13, a synthetic allosteric modifier of hemoglobin that increases P(50), to study the role of altered hemoglobin O ... Full text Link to item Cite

Tracking brain volume changes in C57BL/6J and ApoE-deficient mice in a model of neurodegeneration: a 5-week longitudinal micro-MRI study.

Journal Article Neuroimage · December 2001 Magnetic resonance imaging (MRI)-based volume measurements of brain structures are useful indicators of pending cognitive decline in humans suffering from neurodegenerative diseases. Transgenic mouse models that mimic the clinical conditions of these disor ... Full text Link to item Cite

Neuroprotection from delayed postischemic administration of a metalloporphyrin catalytic antioxidant.

Journal Article J Neurosci · July 1, 2001 Reactive oxygen species contribute to ischemic brain injury. This study examined whether the porphyrin catalytic antioxidant manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) reduces oxidative stress and improves outcome from ... Full text Link to item Cite

Extracellular superoxide dismutase overexpression improves behavioral outcome from closed head injury in the mouse.

Journal Article J Neurotrauma · June 2001 Oxidative stress is known to play an important role in the response of brain to traumatic insults. We tested the hypothesis that increased extracellular superoxide dismutase (EC-SOD) expression can reduce injury in a mouse model of closed head injury. Neur ... Full text Link to item Cite

Effects of metalloporphyrin catalytic antioxidants on rodent focal ischemic brain damage

Journal Article FREE RADICAL BIOLOGY AND MEDICINE · January 1, 2001 Link to item Cite

Species-specific hemodynamic effects of metalloporphyrin SOD mimetics

Journal Article FREE RADICAL BIOLOGY AND MEDICINE · January 1, 2001 Link to item Cite

Changes in protein expression after a superoxide dismutase mimetic in stroke.

Journal Article FREE RADICAL BIOLOGY AND MEDICINE · January 1, 2001 Link to item Cite

Periischemic cerebral blood flow (CBF) does not explain beneficial effects of isoflurane on outcome from near-complete forebrain ischemia in rats.

Journal Article Anesthesiology · October 2000 BACKGROUND: Isoflurane improves outcome from near-complete forebrain ischemia in rats compared with fentanyl-nitrous oxide (N2O). Sympathetic ganglionic blockade with trimethaphan abolishes this beneficial effect. To evaluate whether anesthesia-related dif ... Full text Link to item Cite

A comparison of strain-related susceptibility in two murine recovery models of global cerebral ischemia.

Journal Article Brain Res · June 16, 2000 Genetically engineered mice are increasingly important in stroke research. The strains on which these constructs are built are known to have inherent differential sensitivities to ischemic insults. This has been largely attributed to differences in vascula ... Full text Link to item Cite

Mice overexpressing extracellular superoxide dismutase have increased resistance to global cerebral ischemia.

Journal Article Exp Neurol · June 2000 Transgenic mice, which exhibit a fivefold increase in brain parenchymal extracellular superoxide dismutase (EC-SOD) activity, were used to investigate the role of EC-SOD in global ischemic brain injury. Halothane-anesthetized normothermic wild-type (n = 22 ... Full text Link to item Cite

Extracellular superoxide dismutase deficiency worsens outcome from focal cerebral ischemia in the mouse.

Journal Article Neurosci Lett · May 21, 1999 The role of endogenous extracellular superoxide dismutase (EC-SOD) was examined in a murine model of transient focal cerebral ischemia. Homozygous EC-SOD deficient (EC-SOD-/-; n = 18) and wild type (EC-SOD+/+; n = 19) littermates were anesthetized with hal ... Full text Link to item Cite

Effects of RSR13, a synthetic allosteric modifier of hemoglobin, alone and in combination with dizocilpine, on outcome from transient focal cerebral ischemia in the rat.

Journal Article Brain Res · May 1, 1999 This study examined the effect of a pharmacologically induced rightward shift in the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) on outcome from transient focal cerebral ischemia in the rat. Halothane anesthetized rats (n=20 pe ... Full text Link to item Cite

Apolipoprotein E deficiency worsens outcome from global cerebral ischemia in the mouse.

Journal Article Stroke · May 1999 BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) has been found relevant in a variety of central nervous system disorders. This experiment examined the effect of endogenous murine apoE on selective neuronal necrosis resulting from a transient forebrain isch ... Full text Link to item Cite

Characterization of a recovery global cerebral ischemia model in the mouse.

Journal Article J Neurosci Methods · April 1, 1999 Transgenic/knockout murine variants allow roles of specific proteins to be studied in cerebral ischemia. Because of the size of mice, however, study of prolonged recovery from global ischemia has been limited. This project characterized an adaptation of th ... Full text Link to item Cite

Effects of postischemic halothane administration on outcome from transient focal cerebral ischemia in the rat.

Journal Article J Neurosurg Anesthesiol · January 1999 This study examined the effect of prolonged postischemic halothane administration on outcome from transient focal cerebral ischemia in rats. Conscious normothermic rats were subjected to 75 minutes of filament middle cerebral artery occlusion (MCAO). Anima ... Full text Link to item Cite

Mice overexpressing extracellular superoxide dismutase have increased resistance to focal cerebral ischemia.

Journal Article Neuroscience · January 1999 Featured Publication Transgenic mice, which had been transfected with the human extracellular superoxide dismutase gene, causing an approximate five-fold increase in brain parenchymal extracellular superoxide dismutase activity, were used to investigate the role of extracellul ... Full text Link to item Cite

The effects of aprotinin on outcome from cerebral ischemia in the rat.

Journal Article Anesth Analg · January 1999 UNLABELLED: The administration of aprotinin has been associated with a reduction in cardiac surgery-related stroke. Intrinsic neuroprotective properties of this drug have not been evaluated in laboratory outcome models of cerebral ischemia. The purpose of ... Full text Link to item Cite

Regional CBF in apolipoprotein E-deficient and wild type mice during focal cerebral ischemia.

Journal Article Neuroreport · August 3, 1998 Apolipoprotein E-(apoE) deficient mice exhibit hypercholesterolemia, accelerated atherosclerosis and increased infarct size after middle cerebral artery occlusion (MCAO). This study examined whether worsened ischemic outcome is attributable to effects of a ... Full text Link to item Cite

Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat.

Journal Article Stroke · August 1998 BACKGROUND AND PURPOSE: Neuronal injury results from an insufficient supply of oxygen to the brain. This experiment examined whether a pharmacologically induced rightward shift of the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) ... Full text Link to item Cite

Relative neuroprotective effects of dizocilpine and isoflurane during focal cerebral ischemia in the rat.

Journal Article Anesth Analg · July 1998 UNLABELLED: Both dizocilpine (MK-801) and isoflurane antagonize glutamatergic neurotransmission. In this study, we examined the relative neuroprotective effects of these drugs administered in equianesthetic doses before the onset of focal cerebral ischemia ... Full text Link to item Cite

Apolipoprotein E isoform-specific differences in outcome from focal ischemia in transgenic mice.

Journal Article J Cereb Blood Flow Metab · April 1998 Apolipoprotein E (apoE), a 34-KD glycosylated lipid-binding protein, is expressed as three common isoforms in humans (E2, E3, or E4). Clinical evidence suggests that the apoE genotype (APOE) may be a risk factor for poor outcome after acute central nervous ... Full text Link to item Cite

Modulation of cerebral blood flow is not the mechanism of neuroprotection in transgenic mice over expressing human extracellular superoxide dismutase (EC-SOD)

Journal Article Critical Care Medicine · January 1, 1998 Introduction: Transgenic mice over expressing human EC-SOD (5-fold increase in brain) that have received a 90 min filament occlusion of the middle cerebral artery (MCAO) have a 27% decrease in infarct volume compared to wild type controls (1). Superoxide ( ... Full text Cite

Comparison of the effects of propofol and pentobarbital on neurologic outcome and cerebral infarct size after temporary focal ischemia in the rat.

Journal Article Anesthesiology · November 1997 BACKGROUND: Although propofol is known to have effects on cerebral physiology similar to the barbiturates, a direct comparison of the relative effects of these drugs on outcome from cerebral ischemia has not been performed. The authors postulated that pent ... Full text Link to item Cite

Apolipoprotein E-deficient mice have increased susceptibility to focal cerebral ischemia.

Journal Article J Cereb Blood Flow Metab · July 1997 Recent evidence suggests that apolipoprotein E (ApoE) plays a role in neurologic disease. This experiment compared the neurologic and histologic outcome of ApoE-deficient mutant and wild-type mice subjected to a 60- or 90-minute episode of middle cerebral ... Full text Link to item Cite