Journal ArticleBJA Open · December 2024
BACKGROUND: We aimed to assess perioperative changes in fibrinogen in the cerebrospinal fluid (CSF), their association with markers of blood-brain barrier breakdown and neuroinflammation, and their association with postoperative delirium severity. METHODS: ...
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ConferencePain · August 1, 2024
Postoperative pain is a major clinical problem imposing a significant burden on patients and society. In a survey 2 years after orthopedic surgery, 57% of patients reported persisting postoperative pain. However, only limited progress has been made in the ...
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Journal ArticleAdv Neurobiol · 2024
Microglia, brain-resident innate immune cells, have been extensively studied in neurodegenerative contexts like Alzheimer's disease. The Coronavirus disease 2019 (COVID-19) pandemic highlighted how peripheral infection and inflammation can be detrimental t ...
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Journal ArticleAnn Neurol · December 2023
OBJECTIVE: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain bar ...
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Journal ArticleACS Appl Nano Mater · August 25, 2023
Despite limited evidence for infection of SARS-CoV-2 in the central nervous system, cognitive impairment is a common complication reported in "recovered" COVID-19 patients. Identification of the origins of these neurological impairments is essential to inf ...
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Journal ArticleMol Neurodegener · June 5, 2023
Peripheral inflammation, defined as inflammation that occurs outside the central nervous system, is an age-related phenomenon that has been identified as a risk factor for Alzheimer's disease. While the role of chronic peripheral inflammation has been well ...
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Journal ArticlemedRxiv · May 10, 2023
OBJECTIVE: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain bar ...
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Journal ArticleAlzheimers Dement · May 2023
Delirium is a common, morbid, and costly syndrome that is closely linked to Alzheimer's disease (AD) and AD-related dementias (ADRD) as a risk factor and outcome. Human studies of delirium have advanced our knowledge of delirium incidence and prevalence, r ...
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Journal ArticleBr J Anaesth · February 2023
BACKGROUND: Peripheral surgical trauma can trigger neuroinflammation and ensuing neurological complications, such as delirium. The mechanisms whereby surgery contributes to postoperative neuroinflammation remain unclear and without effective therapies. Her ...
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Journal ArticleBrain Behav Immun Health · December 2022
Delirium is a common postoperative neurologic complication among older adults. Despite its prevalence (14%-50%) and likely association with inflammation, the exact mechanisms that underpin postoperative delirium are unclear. This project aimed to character ...
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Journal ArticleBr J Anaesth · August 2022
Systemic perturbations such as peripheral surgical trauma induce neurovascular, inflammatory, and cognitive changes. The blood-brain barrier is a key interface between the periphery and the central nervous system, and is critically involved in regulating n ...
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Journal ArticleBrain Behav Immun Health · July 2022
Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained ...
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Journal ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology · June 2022
Systemic perturbations can drive a neuroimmune cascade after surgical trauma, including affecting the blood-brain barrier (BBB), activating microglia, and contributing to cognitive deficits such as delirium. Delirium superimposed on dementia (DSD) is a par ...
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Journal ArticleAlzheimers Dement · May 2022
COVID-19 causes lasting neurological symptoms in some survivors. Like other infections, COVID-19 may increase risk of cognitive impairment. This perspective highlights four knowledge gaps about COVID-19 that need to be filled to avoid this possible health ...
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Journal ArticleFront Immunol · 2022
Neuroinflammation is a growing hallmark of perioperative neurocognitive disorders (PNDs), including delirium and longer-lasting cognitive deficits. We have developed a clinically relevant orthopedic mouse model to study the impact of a common surgical proc ...
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Journal ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021
BACKGROUND: Millions of Americans live with Alzheimer's disease (AD) and routinely require common surgical interventions, such as orthopedic surgery. However, these potentially life-saving procedures often increase the risk for further cognitive complicati ...
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Journal ArticleSci Rep · February 4, 2021
Arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) derived lipids play key roles in initiating and resolving inflammation. Neuro-inflammation is thought to play a causal role in perioperative neurocognitive disorders, yet th ...
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Journal ArticleJ Alzheimers Dis · 2021
BACKGROUND: Postoperative cognitive dysfunction (POCD), a syndrome of cognitive deficits occurring 1-12 months after surgery primarily in older patients, is associated with poor postoperative outcomes. POCD is hypothesized to result from neuroinflammation; ...
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Journal Article · 2021
Systemic perturbations can drive a neuroimmune cascade after surgical trauma, including affecting the blood-brain barrier (BBB), activating microglia, and contributing to cognitive deficits such as delirium. Delirium superimposed on dementia (DSD) is a par ...
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Journal ArticleFront Cell Neurosci · 2021
Perioperative neurocognitive disorders (PNDs) are a common complication following procedures such as orthopedic surgery. Using a mouse model of tibial fracture and repair surgery, we have previously shown an increase in neuroinflammation and hippocampal-de ...
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Journal ArticleTrends Neurosci · December 2020
Brain functioning and high-order cognitive functions critically rely on glucose as a metabolic substrate. In a recent study, Kealy et al. investigated the impact of glucose availability on sickness behavior and delirium in mice and humans. They identified ...
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Journal ArticleNat Immunol · November 2020
Featured Publication
Injury is a key driver of inflammation, a critical yet necessary response involving several mediators that is aimed at restoring tissue homeostasis. Inflammation in the central nervous system can be triggered by a variety of stimuli, some intrinsic to the ...
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Journal ArticleNeurosci Biobehav Rev · May 2020
The vagus nerve coordinates most physiologic functions including the cardiovascular and immune systems. This mechanism has significant clinical implications because electrical stimulation of the vagus nerve can control inflammation and organ injury in infe ...
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Journal ArticleAlzheimers Dement · May 2020
Featured Publication
OBJECTIVE: The present work evaluates the relationship between postoperative immune and neurovascular changes and the pathogenesis of surgery-induced delirium superimposed on dementia. BACKGROUND AND RATIONALE: Postoperative delirium is a common complicati ...
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Journal ArticleAnesthesiology · January 2020
The purpose of this article is to provide a succinct summary of the different experimental approaches that have been used in preclinical postoperative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended t ...
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Journal ArticleJ Alzheimers Dis · 2020
BACKGROUND: Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened long-term postoperative cognitive trajectory is the A ...
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Journal Article · 2020
Neuroinflammation is a growing hallmark of perioperative neurocognitive disorders (PNDs), including delirium and longer-lasting cognitive deficits. We have developed a clinically-relevant orthopedic mouse model to study the impact of a common surgical proc ...
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Journal ArticleJ Neuroinflammation · October 28, 2019
BACKGROUND: Patients with pre-existing neurodegenerative disease commonly experience fractures that require orthopedic surgery. Perioperative neurocognitive disorders (PND), including delirium and postoperative cognitive dysfunction, are serious complicati ...
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Journal ArticleAnesthesiology · June 2019
BACKGROUND: Cognitive decline after cardiac surgery occurs frequently and persists in a significant proportion of patients. Preclinical studies and human trials suggest that intravenous lidocaine may confer protection in the setting of neurologic injury. I ...
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Journal ArticleJ Am Geriatr Soc · April 2019
BACKGROUND/OBJECTIVES: Every year, up to 40% of the more than 16 million older Americans who undergo anesthesia/surgery develop postoperative cognitive dysfunction (POCD) or delirium. Each of these distinct syndromes is associated with decreased quality of ...
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Journal ArticleAnesth Analg · April 2019
Neuroinflammation has become a key hallmark of neurological complications including perioperative pathologies such as postoperative delirium and longer-lasting postoperative cognitive dysfunction. Dysregulated inflammation and neuronal injury are emerging ...
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Journal ArticleBr J Anaesth · March 2019
BACKGROUND: Resolution of inflammation is an active and dynamic process after surgery. Maresin 1 (MaR1) is one of a growing number of specialised pro-resolving lipids biosynthesised by macrophages that regulates acute inflammation. We investigated the effe ...
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Journal Article · February 2019
Abstract Perioperative neurocognitive disorders (PND), including delirium and postoperative cognitive dysfunction, are serious complications that afflict up to 50% of surgical patients and for which there are no disease-modifying therapeutic options. Here, ...
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Journal ArticleBrain Stimul · 2019
Featured Publication
BACKGROUND: The vagus nerve is involved in regulating immunity and resolving inflammation. Current strategies aimed at modulating neuroinflammation and cognitive decline, in many cases, are limited and ineffective. OBJECTIVE: We sought to develop a minimal ...
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Journal ArticleFront Neurosci · 2019
Neuroinflammation initiated by damage-associated molecular patterns, including high mobility group box 1 protein (HMGB1), has been implicated in adverse neurological outcomes following lethal hemorrhagic shock and polytrauma. Emergency preservation and res ...
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Journal ArticleAdv Exp Med Biol · 2019
Surgery can be a life-saving procedure; however, significant complications may occur after routine procedures especially in older and more frail patients. Perioperative neurocognitive disorders (PNDs), including delirium and postoperative cognitive dysfunc ...
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Journal ArticleFront Immunol · 2019
Postoperative delirium is a frequent and debilitating complication, especially amongst high risk procedures such as orthopedic surgery, and its pathogenesis remains unclear. Inattention is often reported in the clinical diagnosis of delirium, however limit ...
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Book · January 1, 2019
Perioperative neurocognitive disorders are the most common and least recognized complications of anesthesia and surgery in older patients. This book represents the first unified source of information on this group of disorders, serving as a practical guide ...
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Journal ArticleAnesth Analg · December 2018
As part of the American Society of Anesthesiology Brain Health Initiative goal of improving perioperative brain health for older patients, over 30 experts met at the fifth International Perioperative Neurotoxicity Workshop in San Francisco, CA, in May 2016 ...
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Journal ArticleBr J Anaesth · November 2018
Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological tes ...
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Journal ArticleActa Anaesthesiol Scand · November 2018
Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological tes ...
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Journal ArticleAnesth Analg · November 2018
Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological tes ...
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Journal ArticleAnesthesiology · October 2018
For half a century, it has been known that some patients experience neurocognitive dysfunction after cardiac surgery; however, defining its incidence, course, and causes remains challenging and controversial. Various terms have been used to describe neuroc ...
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Journal ArticleJ Neuroinflammation · September 4, 2018
BACKGROUND: The complement system plays an important role in many neurological disorders. Complement modulation, including C3/C3a receptor signaling, shows promising therapeutic effects on cognition and neurodegeneration. Yet, the implications for this pat ...
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Journal ArticleBrain Behav Immun · August 2018
p38 mitogen-activated protein kinase (MAPK) consists of two major isoforms: p38α and p38β; however, it remains unclear which isoform is more important for chronic pain development. Recently, we developed potent, long-lasting, and p38 MAPK subtype-specific ...
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Journal ArticleAnesthesiology · August 2018
Chronic pain is maintained in part by central sensitization, a phenomenon of synaptic plasticity, and increased neuronal responsiveness in central pain pathways after painful insults. Accumulating evidence suggests that central sensitization is also driven ...
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Journal ArticleAnesthesiology · April 2018
BACKGROUND: Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patie ...
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Journal ArticleJ Vis Exp · February 27, 2018
Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and significantly diminish the outcome. Indeed, after routine orthopedic surgery to repair a fracture, as m ...
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Journal ArticleJ Neurosci · January 10, 2018
Immune-related events in the periphery can remotely affect brain function, contributing to neurodegenerative processes and cognitive decline. In mice, peripheral surgery induces a systemic inflammatory response associated with changes in hippocampal synapt ...
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Journal ArticleFront Pharmacol · 2018
Mechanisms of pain resolution are largely unclear. Increasing evidence suggests that specialized pro-resolving mediators (SPMs), derived from fish oil docosahexaenoic acid (DHA), promote the resolution of acute inflammation and potently inhibit inflammator ...
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Journal ArticleRedox Biol · October 2017
Ischemia-reperfusion (IR) injury involves complex pathological processes in which reduction of nitric oxide (NO) bioavailability is suggested as a key factor. Inorganic nitrate can form NO in vivo via NO synthase-independent pathways and may thus provide b ...
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Journal ArticleAnn Neurol · April 2017
OBJECTIVE: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack informati ...
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Journal ArticleFront Immunol · 2017
Resolution agonists, including lipid mediators and peptides such as annexin A1 (ANXA1), are providing novel approaches to treat inflammatory conditions. Surgical trauma exerts a significant burden on the immune system that can affect and impair multiple or ...
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Journal ArticleFront Immunol · 2017
Alzheimer's disease (AD) remains the leading cause of dementia worldwide, and over the last several decades, the role of inflammation in the pathogenesis of this neurodegenerative disorder has been increasingly elucidated. The initiation of the acute infla ...
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Journal ArticleProc Natl Acad Sci U S A · October 25, 2016
Pain is a critical component hindering recovery and regaining of function after surgery, particularly in the elderly. Understanding the role of pain signaling after surgery may lead to novel interventions for common complications such as delirium and posto ...
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Journal ArticleJ Neuroinflammation · October 12, 2016
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially amongst elderly patients. Neuroinflammation and iron homeostasis are key hallmarks of several neurological disorders. In this study, we investigated t ...
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Journal ArticleJ Neuroinflammation · August 30, 2016
BACKGROUND: Postoperative delirium is prevalent in older patients and associated with worse outcomes. Recent data in animal studies demonstrate increases in inflammatory markers in plasma and cerebrospinal fluid (CSF) even after aseptic surgery, suggesting ...
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Journal ArticleJ Am Heart Assoc · July 18, 2016
BACKGROUND: Early-life reduction in nephron number (uninephrectomy [UNX]) and chronic high salt (HS) intake increase the risk of hypertension and chronic kidney disease. Adenosine signaling via its different receptors has been implicated in modulating rena ...
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Journal ArticleAnesthesiology · May 2016
Inflammation and immunity are regulated by neural reflexes. Recent basic science research has demonstrated that a neural reflex, termed the inflammatory reflex, modulates systemic and regional inflammation in a multiplicity of clinical conditions encounter ...
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Journal ArticleToxicol Sci · January 2016
The possibility that exposure to general anesthetics during early life results in long-term impairment of neural function attracted considerable interest over the past decade. Extensive laboratory data suggest that administration of these drugs during crit ...
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Journal ArticlePaediatr Anaesth · January 2016
UNLABELLED: Preclinical evidence suggests that anesthetic agents harm the developing brain thereby causing long-term neurocognitive impairments. It is not clear if these findings apply to humans, and retrospective epidemiological studies thus far have fail ...
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Journal ArticleFront Aging Neurosci · 2016
Systemic inflammation, for example as a result of infection, often contributes to long-term complications. Neuroinflammation and cognitive decline are key hallmarks of several neurological conditions, including advance age. The contribution of systemic inf ...
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Journal ArticleFront Immunol · 2016
Postoperative neurocognitive disorders are common complications in elderly patients following surgery or critical illness. High mobility group box 1 protein (HMGB1) is rapidly released after tissue trauma and critically involved in response to sterile inju ...
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Journal ArticleAnesthesiol Clin · September 2015
Postoperative cognitive dysfunction (POCD) is a common complication associated with significant morbidity and mortality in elderly patients. There is much interest in and controversy about POCD, reflected partly in the increasing number of articles publish ...
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Journal ArticleFree Radic Biol Med · June 2015
Oxidative stress contributes to the pathogenesis of many disorders, including diabetes and cardiovascular disease. Immune cells are major sources of superoxide (O2(∙-)) as part of the innate host defense system, but exaggerated and sustained O2(∙-) generat ...
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Journal ArticleMol Med · March 17, 2015
Surgery and critical illness often associate with cognitive decline. Surgical trauma or infection can lead independently to learning and memory impairments via similar, but not identical, cellular signaling of the innate immune system that promotes neuroin ...
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Journal ArticleAnesth Analg · March 2015
To learn the latest developments in the various forms of postoperative cognitive dysfunction, a group of scientists and physicians met in Stockholm for a full day of presentations and interactive discussions. This article summarizes the discussion; highlig ...
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Journal ArticleJ Alzheimers Dis · 2015
In this review we discuss the immunopathology of Alzheimer's disease (AD) and recent advances in the prevention of minor cognitive impairment (MCI) by nutritional supplementation with omega-3 fatty acids. Defective phagocytosis of amyloid-β (Aβ) and abnorm ...
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Journal ArticleBrain Behav Immun · February 2014
Exposure to infections in early life is considered a risk-factor for developing schizophrenia. Recently we reported that a neonatal CNS infection with influenza A virus in mice resulted in a transient induction of the brain kynurenine pathway, and subseque ...
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Journal ArticlePLoS One · 2014
Inflammation is a hallmark of several disease states ranging from neurodegeneration to sepsis but is also implicated in physiological processes like ageing. Non-resolving inflammation and prolonged neuroinflammation are unclear processes implicated in seve ...
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Journal ArticleFASEB J · September 2013
Hospitalization for major surgery or critical illness often associates with cognitive decline. Inflammation and dysregulation of the innate immune system can exert broad effects in the periphery and central nervous system (CNS), yet the mechanisms underlyi ...
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Journal ArticleAnesthesiology · May 2013
BACKGROUND: Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that ...
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Journal ArticleMol Med · February 8, 2013
The cholinergic antiinflammatory pathway (CAP), which terminates in the spleen, attenuates postoperative cognitive decline (PCD) in rodents. Surgical patients with metabolic syndrome exhibit exaggerated and persistent PCD that is reproduced in postoperativ ...
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Journal ArticleCNS Neurosci Ther · December 2012
AIM: Postoperative cognitive dysfunction (POCD) is a growing and largely underestimated problem without defined etiology. Herein, we sought to determine the relationship between cognitive decline, blood-brain barrier (BBB) permeability, and inflammation, n ...
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Journal ArticlePLoS One · 2012
It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE). Many women use some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used as analgesics at su ...
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Journal ArticleAnn Neurol · December 2011
OBJECTIVE: Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to un ...
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Journal ArticleMayo Clin Proc · September 2011
Elderly patients who have an acute illness or who undergo surgery often experience cognitive decline. The pathophysiologic mechanisms that cause neurodegeneration resulting in cognitive decline, including protein deposition and neuroinflammation, also play ...
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Journal ArticleCrit Care · June 24, 2011
INTRODUCTION: Acute kidney injury following surgery incurs significant mortality with no proven preventative therapy. We investigated whether the α2 adrenoceptor agonist dexmedetomidine (Dex) provides protection against ischemia-reperfusion induced kidney ...
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Journal ArticleBrain Res · April 6, 2011
We have designed a clinically relevant model of perinatal asphyxia providing intrapartum hypoxia in rats. On gestation day 22 SD rats were anesthetized and the uterine horns were exteriorized and placed in a water bath at 37°C for up to 20min. After this, ...
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Journal ArticleProc Natl Acad Sci U S A · November 23, 2010
Cognitive decline following surgery in older individuals is a major clinical problem of uncertain mechanism; a similar cognitive decline also follows severe infection, chemotherapy, or trauma and is currently without effective therapy. A variety of mechani ...
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Journal ArticleAnn Neurol · September 2010
OBJECTIVE: Although postoperative cognitive dysfunction (POCD) often complicates recovery from major surgery, the pathogenic mechanisms remain unknown. We explored whether systemic inflammation, in response to surgical trauma, triggers hippocampal inflamma ...
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Journal ArticleCrit Care · 2010
INTRODUCTION: The impact of pro-inflammatory cytokines on neuroinflammation and cognitive function after lipopolysaccharide (LPS) challenge remains elusive. Herein we provide evidence that there is a temporal correlation between high-mobility group box 1 ( ...
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