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The kynurenine pathway in traumatic brain injuries and concussion

FRONTIERS IN NEUROLOGY (2023)

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NLRP3 inflammasome in traumatic brain injury: Its implication in the disease pathophysiology and potential as a therapeutic target

Rohan Chakraborty et al.

Summary: Traumatic brain injury (TBI) caused by head trauma has significant consequences in terms of disability and healthcare cost. Neuroinflammation, particularly through the NLRP3 inflammasome, plays a crucial role in TBI. Inhibitors of the NLRP3 inflammasome show potential in reducing neuroinflammation and improving cognitive and motor function in TBI. However, clinical trials are needed to evaluate the efficacy of these promising therapeutic candidates.

LIFE SCIENCES (2023)

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Article Psychiatry

Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-traumatic brain injury anxiety and social impairment

Dmitry Frank et al.

Summary: Traumatic brain injury (TBI) is a serious condition that has long-term psychiatric consequences. Blood glutamate scavengers (BGS) such as pyruvate have been shown to effectively treat TBI and its psychiatric sequelae. This study evaluated the use of pyruvate as a treatment for TBI-related neuropsychiatric conditions in a rat model, showing positive results in reducing brain glutamate levels and improving behavioral symptoms.

TRANSLATIONAL PSYCHIATRY (2023)

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Review Immunology

α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect

Huiyang Liu et al.

Summary: Depression is related to neurotransmitters and dysfunctions in various systems, and the hypothesis of monoamine neurotransmitters is commonly recognized. However, drugs based on this hypothesis have not been successful in treating depression. Recent research suggests that depression and inflammation are strongly linked, and activating the cholinergic anti-inflammatory pathway through alpha 7 nAChR shows promise in treating depression. This review explores the correlations between inflammation and depression, as well as the role of alpha 7 nAChR in the cholinergic system.

JOURNAL OF NEUROINFLAMMATION (2023)

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Review Neurosciences

Emotion Dysregulation Following Trauma: Shared Neurocircuitry of Traumatic Brain Injury and Trauma-Related Psychiatric Disorders

Carissa N. Weis et al.

Summary: The psychological trauma associated with traumatic brain injury (TBI) is an important and often overlooked factor that can hinder brain recovery and worsen mental health. Emotion dysregulation is a common factor leading to poor cognitive and affective outcomes following TBI. Research on emotion regulation neural circuits can provide insights into treatment and early intervention strategies to prevent the adverse consequences of TBI.

BIOLOGICAL PSYCHIATRY (2022)

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Review Neurosciences

The Kynurenine Pathway in Traumatic Brain Injury: Implications for Psychiatric Outcomes

Timothy B. Meier et al.

Summary: Traumatic brain injury (TBI) is a risk factor for psychiatric disorders, with inflammation and the dysregulation of the kynurenine pathway (KP) playing a role. Increased production of neurotoxic kynurenines such as quinolinic acid in TBI is associated with negative prognosis, including death, imaging abnormalities, and increased depressive and anxiety symptoms. Imbalance in KP metabolism may contribute to the development of psychiatric sequelae after TBI.

BIOLOGICAL PSYCHIATRY (2022)

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Review Clinical Neurology

Cognitive Impairment in Primary and Secondary Headache Disorders

Olivia Begasse de Dhaem et al.

Summary: This article reviews the recent literature on cognitive impairment and headache. Migraine is associated with deficits in attention, executive function, processing speed, and memory, but not with dementia. Tension-type headache does not seem to be associated with cognitive dysfunction. Cluster headache in early to midlife may be associated with executive dysfunction. Several secondary headache syndromes are related to poorer cognitive performance or distinctive cognitive patterns.

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Article Clinical Neurology

Association between microglial activation and serum kynurenine pathway metabolites in multiple sclerosis patients

Maija Saraste et al.

Summary: This clinical study found an association between low serum 3-hydroxykynurenine levels and increased microglial activation in the brains of multiple sclerosis patients.

MULTIPLE SCLEROSIS AND RELATED DISORDERS (2022)

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Article Neurosciences

Blast-related traumatic brain injury is mediated by the kynurenine pathway

Yu Zhang et al.

Summary: The overactivation of the kynurenine pathway is observed in blast-related traumatic brain injury, and inhibitors of key enzymes in this pathway show a protective effect in reducing the damage. Specifically, the KMO inhibitor exhibits significant neuroprotective properties in this type of brain injury.

NEUROREPORT (2022)

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Article Immunology

Positive association between serum quinolinic acid and functional connectivity following concussion

Timothy B. Meier et al.

Summary: This study found a positive association between elevated QuinA levels and functional connectivity strength in concussed athletes with prior concussion. Additionally, concussed athletes who reported depressive symptoms on the first day post-injury had significantly higher global connectivity strength.

BRAIN BEHAVIOR AND IMMUNITY (2021)

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Review Biochemistry & Molecular Biology

DAMPs and RAGE Pathophysiology at the Acute Phase of Brain Injury: An Overview

Baptiste Balanca et al.

Summary: Early brain injury leads to the release of damage-associated molecular patterns (DAMPs), which may trigger cellular damage and non-infectious inflammation, exacerbating brain injury.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Pharmacology & Pharmacy

Indoleamine and tryptophan 2,3-dioxygenases as important future therapeutic targets

Ana Dolsak et al.

Summary: This review discusses the key step of tryptophan metabolism and the importance of relevant enzymes in pathological conditions. In recent years, many inhibitors targeting these enzymes have been developed, and these inhibitors have entered clinical trials.

PHARMACOLOGY & THERAPEUTICS (2021)

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Review Clinical Neurology

Ketamine's effect on inflammation and kynurenine pathway in depression: A systematic review

Emma Kopra et al.

Summary: Ketamine appears to induce anti-inflammatory effects in at least a proportion of depressed patients, with strong support from rodent studies. Clinical evidence is less robust, but most experiments also demonstrated decreases in peripheral inflammation. Further research is recommended to investigate markers in the central nervous system and examine the clinical relevance of inflammatory changes.

JOURNAL OF PSYCHOPHARMACOLOGY (2021)

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Article Endocrinology & Metabolism

Long term neuroprotective effects of acute single dose MK-801treatment against traumatic brain injury in immature rats

Ayse Cigel et al.

Summary: The study investigates the long-term effects of MK-801 on hippocampal damage, locomotor activity, and cognitive functions in immature rats following traumatic brain injury. Results show that MK-801 significantly ameliorated trauma-induced hippocampal neuron loss and increased expressions of BDNF, NGF, NMDA-R, and GFAP in hippocampal regions. Furthermore, treatment with MK-801 reduced anxiety and improved hippocampus-dependent memory in animals after TBI, indicating its neuroprotective role against trauma-induced hippocampal neuron loss and associated cognitive impairment in rats.

NEUROPEPTIDES (2021)

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Article Immunology

Prospective study of the effects of sport-related concussion on serum kynurenine pathway metabolites

Timothy B. Meier et al.

BRAIN BEHAVIOR AND IMMUNITY (2020)

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Article Biochemistry & Molecular Biology

Cerebrospinal Fluid Neurofilament Light Chain Is Associated with Kynurenine Pathway Metabolite Changes in Multiple Sclerosis

Cecilia Rajda et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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The Gut Microbiota, Kynurenine Pathway, and Immune System Interaction in the Development of Brain Cancer

Mona Dehhaghi et al.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2020)

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Cellular infiltration in traumatic brain injury

Aftab Alam et al.

JOURNAL OF NEUROINFLAMMATION (2020)

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Systematic Review on the Involvement of the Kynurenine Pathway in Stroke: Pre-clinical and Clinical Evidence

Gabriela D. Colpo et al.

FRONTIERS IN NEUROLOGY (2019)

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Article Neurosciences

Microorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health Status

Mona Dehhaghi et al.

INTERNATIONAL JOURNAL OF TRYPTOPHAN RESEARCH (2019)

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IDO and TDO as a potential therapeutic target in different types of depression

Yanjie Qin et al.

METABOLIC BRAIN DISEASE (2018)

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Centers for Disease Control and Prevention Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury Among Children

Angela Lumba-Brown et al.

JAMA PEDIATRICS (2018)

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Andrew I. R. Maas et al.

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The far-reaching scope of neuroinflammation after traumatic brain injury

Dennis W. Simon et al.

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Involvement of the kynurenine pathway in the pathogenesis of Parkinson's disease

Chai K. Lim et al.

PROGRESS IN NEUROBIOLOGY (2017)

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Abnormalities in Kynurenine Pathway Metabolism in Treatment-Resistant Depression and Suicidality: A Systematic Review

Gianluca Serafini et al.

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Mood symptoms correlate with kynurenine pathway metabolites following sports-related concussion

Rashmi Singh et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2016)

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Article Immunology

Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder

Timothy B. Meier et al.

BRAIN BEHAVIOR AND IMMUNITY (2016)

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Article Pharmacology & Pharmacy

The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia

Maria Isabel Cuartero et al.

CURRENT PHARMACEUTICAL DESIGN (2016)

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Article Psychiatry

An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation

L. Brundin et al.

TRANSLATIONAL PSYCHIATRY (2016)

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Article Psychiatry

Neurotoxic kynurenine metabolism is increased in the dorsal hippocampus and drives distinct depressive behaviors during inflammation

J. M. Parrott et al.

TRANSLATIONAL PSYCHIATRY (2016)

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Article Medicine, General & Internal

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Kaj Blennow et al.

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Article Immunology

Activation of the kynurenine pathway and increased production of the excitotoxin quinolinic acid following traumatic brain injury in humans

Edwin B. Yan et al.

JOURNAL OF NEUROINFLAMMATION (2015)

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Article Multidisciplinary Sciences

Expression of the Kynurenine Pathway in Human Peripheral Blood Mononuclear Cells: Implications for Inflammatory and Neurodegenerative Disease

Simon P. Jones et al.

PLOS ONE (2015)

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Reduction of Brain Kynurenic Acid Improves Cognitive Function

Rouba Kozak et al.

JOURNAL OF NEUROSCIENCE (2014)

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Article Pharmacology & Pharmacy

Kynurenic acid as an antagonist of α7 nicotinic acetylcholine receptors in the brain: Facts and challenges

Edson X. Albuquerque et al.

BIOCHEMICAL PHARMACOLOGY (2013)

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Kynurenic acid, by targeting 7 nicotinic acetylcholine receptors, modulates extracellular GABA levels in the rat striatum in vivo

Sarah Beggiato et al.

EUROPEAN JOURNAL OF NEUROSCIENCE (2013)

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Review Cell Biology

Quinolinic Acid: An Endogenous Neurotoxin with Multiple Targets

Rafael Lugo-Huitron et al.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2013)

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Review Biochemistry & Molecular Biology

Quinolinic acid, the inescapable neurotoxin

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Kynurenines in the mammalian brain: when physiology meets pathology

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Kynurenine Pathway in Schizophrenia: Pathophysiological and Therapeutic Aspects

Norbert Mueller et al.

CURRENT PHARMACEUTICAL DESIGN (2011)

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Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?

Johann Steiner et al.

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Kynurenine and its metabolites in Alzheimer's disease patients

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In Situ Detection of Inflammatory Mediators in Post Mortem Human Brain Tissue after Traumatic Injury

Tony Frugier et al.

JOURNAL OF NEUROTRAUMA (2010)

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Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

Jenna M. Ziebell et al.

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The Kynurenine Pathway and Inflammation in Amyotrophic Lateral Sclerosis

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Effect of quinolinic acid on human astrocytes morphology and functions: implications in Alzheimer's disease

Ka Ka Ting et al.

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Mechanism for Quinolinic Acid Cytotoxicity in Human Astrocytes and Neurons

Nady Braidy et al.

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Andrew I. R. Maas et al.

LANCET NEUROLOGY (2008)

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Robert Dantzer et al.

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The involvement of astrocytes and kynurenine pathway in Alzheimer's disease

Ka Ka Ting et al.

NEUROTOXICITY RESEARCH (2007)

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C. Werner et al.

BRITISH JOURNAL OF ANAESTHESIA (2007)

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Kynurenine pathway in major depression:: Evidence of impaired neuroprotection

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JOURNAL OF AFFECTIVE DISORDERS (2007)

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Article Critical Care Medicine

The effect of the selective NMDA receptor antagonist traxprodil in the treatment of traumatic brain injury

L Yurkewicz et al.

JOURNAL OF NEUROTRAUMA (2005)

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Article Neurosciences

Effects of the dopaminergic agent and NMDA receptor antagonist amantadine on cognitive function, cerebral glucose metabolism and D2 receptor availability in chronic traumatic brain injury: A study using positron emission tomography (PET)

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BRAIN INJURY (2005)

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ATP mediates rapid microglial response to local brain injury in vivo

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NATURE NEUROSCIENCE (2005)

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Quinolinic acid selectively induces apoptosis of human astrocytes: potential role in AIDS dementia complex

Gilles J. Guillemin et al.

JOURNAL OF NEUROINFLAMMATION (2005)

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Involvement of quinolinic acid in AIDS dementia complex

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NEUROTOXICITY RESEARCH (2005)

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Prognosis for mild traumatic brain injury:: Results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury

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JOURNAL OF REHABILITATION MEDICINE (2004)

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Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes

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NEUROCHEMISTRY INTERNATIONAL (2002)

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Implications of the kynurenine pathway and quinolinic acid in Alzheimer's disease

GJ Guillemin et al.

REDOX REPORT (2002)

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Article Biochemistry & Molecular Biology

Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection

GJ Guillemin et al.

JOURNAL OF NEUROCHEMISTRY (2001)

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