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References from P2X7 receptor-mediated IL-1β release by human brain tissue: the impact of CNS-penetrant potential therapeutics. Local targets link to admitted publications; unresolved targets remain external evidence.
Incidence of traumatic brain injury across the full disease spectrum: A population-based medical record review study
10.1097/ede.0b013e318231d535 · 2011 · External reference
Costs of nonfatal traumatic brain injury in the United States, 2016
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Traumatic brain injury: An overview of epidemiology, pathophysiology, and medical management
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Traumatic brain injury: Integrated approaches to improve prevention, clinical care, and research
10.1016/s1474-4422(17)30371-x · 2017 · External reference
Traumatic brain injury
10.1016/s0140-6736(00)02689-1 · 2000 · External reference
Neurosurgical and intensive care management of traumatic brain injury
10.1055/s-0035-1562884 · 2015 · External reference
Paths to successful translation of new therapies for severe traumatic brain injury in the golden age of traumatic brain injury research: A Pittsburgh vision
10.1089/neu.2018.6203 · 2020 · External reference
Traumatic brain injuries
10.1038/nrdp.2016.84 · 2016 · External reference
Role of excitatory amino acid-mediated ionic fluxes in traumatic brain injury
10.1111/j.1750-3639.1995.tb00621.x · 1995 · External reference
Secondary ischemia impairing the restoration of ion homeostasis following traumatic brain injury
10.3171/jns.2005.103.4.0707 · 2005 · External reference
Glutamate and GABA imbalance following traumatic brain injury
10.1007/s11910-015-0545-1 · 2015 · External reference
Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical impact model
10.1111/j.1471-4159.1993.tb07437.x · 1993 · External reference
Traumatic brain injury: Oxidative stress and neuroprotection
10.1089/ars.2012.4981 · 2013 · External reference
Peroxynitrite-mediated protein nitration and lipid peroxidation in a mouse model of traumatic brain injury
10.1089/089771504772695904 · 2004 · External reference
Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury
10.1523/jneurosci.17-19-07415.1997 · 1997 · External reference
Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury
10.1016/j.expneurol.2009.04.030 · 2009 · External reference
Impaired cerebral mitochondrial function after traumatic brain injury in humans
10.3171/jns.2000.93.5.0815 · 2000 · External reference
Microglial activation in traumatic brain injury
10.3389/fnagi.2017.00208 · 2017 · External reference
Microglia activation as a biomarker for traumatic brain injury
10.3389/fneur.2013.00030 · 2013 · External reference
Traumatic brain injury causes chronic cortical inflammation and neuronal dysfunction mediated by microglia
10.1523/jneurosci.2469-20.2020 · 2021 · External reference
Inflammation after trauma: Microglial activation and traumatic brain injury
10.1002/ana.22455 · 2011 · External reference
ATP mediates rapid microglial response to local brain injury in vivo
10.1038/nn1472 · 2005 · External reference
Long-term intracerebral inflammatory response after traumatic brain injury
10.1016/j.forsciint.2004.06.027 · 2004 · External reference
Activation of NF-κB mediates astrocyte swelling and brain edema in traumatic brain injury
10.1089/neu.2013.3169 · 2014 · External reference
Morphological and functional alterations of astrocytes responding to traumatic brain injury
10.31083/j.jin.2019.02.110 · 2019 · External reference
Microglial depletion with CSF1R inhibitor during chronic phase of experimental traumatic brain injury reduces neurodegeneration and neurological deficits
10.1523/jneurosci.2402-19.2020 · 2020 · External reference
Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain
10.4049/jimmunol.156.11.4363 · 1996 · External reference
Transient post-operative overexpression of CXCR2 on monocytes of traumatic brain injury patients drives monocyte chemotaxis toward cerebrospinal fluid and enhances monocyte-mediated immunogenic cell death of neurons in vitro
10.1186/s12974-022-02535-6 · 2022 · External reference
Nonclassical monocytes mediate secondary injury, neurocognitive outcome, and neutrophil infiltration after traumatic brain injury
10.4049/jimmunol.1700896 · 2017 · External reference
Early monitoring and quantitative evaluation of macrophage infiltration after experimental traumatic brain injury: A magnetic resonance imaging and flow cytometric analysis
10.1016/j.mcn.2016.11.008 · 2017 · External reference
Traumatic brain injury induces macrophage subsets in the brain
10.1002/eji.201243084 · 2013 · External reference
Oxidative burst of circulating neutrophils following traumatic brain injury in human
10.1371/journal.pone.0068963 · 2013 · External reference
Neutrophils and the blood–brain barrier dysfunction after trauma
10.1002/med.20064 · 2007 · External reference
Cellular infiltration in traumatic brain injury
10.1186/s12974-020-02005-x · 2020 · External reference
Microdialysis in the human brain and its potential role in the development and clinical assessment of drugs
10.2174/092986707780831113 · 2007 · External reference
Inflammation in human brain injury: Intracerebral concentrations of IL-1alpha, IL-1beta, and their endogenous inhibitor IL-1ra
10.1089/neu.2007.0295 · 2007 · External reference
The cytokine response to human traumatic brain injury: Temporal profiles and evidence for cerebral parenchymal production
10.1038/jcbfm.2010.142 · 2011 · External reference
Inflammatory neuroprotection following traumatic brain injury
10.1126/science.aaf6260 · 2016 · External reference
Principal component analysis of the cytokine and chemokine response to human traumatic brain injury
10.1371/journal.pone.0039677 · 2012 · External reference
Pro-inflammatory and pro-apoptotic elements of the neuroinflammatory response are activated in traumatic brain injury
10.1007/978-3-211-85578-2_85 · 2009 · External reference
Neutralization of interleukin-1β following diffuse traumatic brain injury in the mouse attenuates the loss of mature oligodendrocytes
10.1089/neu.2018.5660 · 2018 · External reference
Experimental brain injury induces expression of interleukin-1β mRNA in the rat brain
10.1016/0169-328x(94)00287-o · 1995 · External reference
Distinct cellular patterns of upregulated chemokine expression supporting a prominent inflammatory role in traumatic brain injury
10.1089/neu.2008.0562 · 2008 · External reference
10.1007/978-3-7091-6837-0_28
10.1007/978-3-7091-6837-0_28 · 1997 · External reference
Neuroinflammation after traumatic brain injury: Opportunities for therapeutic intervention
10.1016/j.bbi.2012.06.008 · 2012 · External reference
Moderate and severe traumatic brain injury in adults
10.1016/s1474-4422(08)70164-9 · 2008 · External reference
The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7)
10.1126/science.272.5262.735 · 1996 · External reference
Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody
10.7554/elife.36217 · 2018 · External reference
A central role for P2X7 receptors in human microglia
10.1186/s12974-018-1353-8 · 2018 · External reference
P2X7 receptors on microglial cells mediate injury to cortical neurons in vitro
10.1002/glia.20379 · 2006 · External reference
Purinergic (P2X7) receptor activation of microglia induces cell death via an interleukin-1-independent mechanism
10.1006/mcne.2001.1054 · 2002 · External reference
The P2X7 receptor drives microglial activation and proliferation: A trophic role for P2X7R pore
10.1523/jneurosci.5512-08.2009 · 2009 · External reference
Increased levels of GFAP and purinergic P2X7 receptor in Alzheimer's disease brain are associated with Aβ, tau pathologies and synaptic loss.
10.1186/s13195-025-01916-2 · 2025 · External reference
Inhibition of P2X7 receptors improves outcomes after traumatic brain injury in rats
10.1007/s11302-017-9579-y · 2017 · External reference
Microglia: Scapegoat, saboteur, or something else?
10.1126/science.1227901 · 2013 · External reference
Immunosuppression after traumatic or ischemic CNS damage: It is neuroprotective and illuminates the role of microglial cells
10.1016/j.pneurobio.2007.12.001 · 2008 · External reference
Microglia at center stage: A comprehensive review about the versatile and unique residential macrophages of the central nervous system
10.18632/oncotarget.23106 · 2017 · External reference
Microglia in neuroinflammation and neurodegeneration: From understanding to therapy
10.3389/fnins.2021.742065 · 2021 · External reference
Microglia biology: One century of evolving concepts
10.1016/j.cell.2019.08.053 · 2019 · External reference
The semantics of microglia activation: Neuroinflammation, homeostasis, and stress
10.1186/s12974-021-02309-6 · 2021 · External reference
The TWIK2 potassium efflux channel in macrophages mediates NLRP3 inflammasome-induced inflammation
10.1016/j.immuni.2018.04.032 · 2018 · External reference
K⁺ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter
10.1016/j.immuni.2013.05.016 · 2013 · External reference
The P2X7 receptor: A key player in IL-1 processing and release
10.4049/jimmunol.176.7.3877 · 2006 · External reference
Modulation of the purinergic P2X7 receptor attenuates lipopolysaccharide-mediated microglial activation and neuronal damage in inflamed brain
10.1523/jneurosci.5417-06.2007 · 2007 · External reference
The human P2X7 receptor alters microglial morphology and cytokine secretion following immunomodulation
10.3389/fphar.2023.1148190 · 2023 · External reference
ILr1β production is dependent on the activation of purinergic receptors and NLRP3 pathway in human macrophages
10.1096/fj.14-267393 · 2015 · External reference
ATP induces the release of IL-1 from LPS-primed cells in vivo
10.4049/jimmunol.154.6.2821 · 1995 · External reference
Ca2+ stores and Ca2+ entry differentially contribute to the release of IL-1β and IL-1α from murine macrophages
10.4049/jimmunol.170.6.3029 · 2003 · External reference
Nonclassical IL-1β secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages
10.4049/jimmunol.179.3.1913 · 2007 · External reference
Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP
10.1038/ncomms10555 · 2016 · External reference
P2X7 receptor differentially couples to distinct release pathways for IL-1β in mouse macrophage
10.4049/jimmunol.180.11.7147 · 2008 · External reference
P2X7 receptor activation leads to NLRP3-independent IL-1β release by human macrophages
10.1186/s12964-023-01356-1 · 2023 · External reference
The role of microglial P2X7: Modulation of cell death and cytokine release
10.1186/s12974-017-0904-8 · 2017 · External reference
Temporal interleukin-1β secretion from primary human peripheral blood monocytes by P2X7-independent and P2X7-dependent mechanisms
10.1074/jbc.m109.072793 · 2010 · External reference
In vivo detection of extracellular adenosine triphosphate in a mouse model of traumatic brain injury
10.1089/neu.2020.7226 · 2021 · External reference
P2X7 receptor modulation on microglial cells and reduction of brain infarct caused by middle cerebral artery occlusion in rat
10.1038/sj.jcbfm.9600250 · 2006 · External reference
P2X7 receptor blockade prevents ATP excitotoxicity in neurons and reduces brain damage after ischemia
10.1016/j.nbd.2011.12.014 · 2012 · External reference
Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus
10.1186/1742-2094-9-69 · 2012 · External reference
Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice
10.1371/journal.pone.0041229 · 2012 · External reference
Involvement of P2X and P2Y receptors in microglial activation in vivo
10.1007/s11302-007-9082-y · 2007 · External reference
Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury
10.1073/pnas.0902531106 · 2009 · External reference
Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567
10.1111/bph.12314 · 2013 · External reference
Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535
10.1016/j.bmcl.2011.04.077 · 2011 · External reference
Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate
10.3899/jrheum.110874 · 2012 · External reference
Recent advances in CNS P2X7 physiology and pharmacology: Focus on neuropsychiatric disorders
10.3389/fphar.2018.00030 · 2018 · External reference
Neuropsychopharmacology of JNJ-55308942: Evaluation of a clinical candidate targeting P2X7 ion channels in animal models of neuroinflammation and anhedonia
10.1038/s41386-018-0141-6 · 2018 · External reference
4-Methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridine-based P2X7 receptor antagonists: Optimization of pharmacokinetic properties leading to the identification of a clinical candidate
10.1021/acs.jmedchem.7b00408 · 2017 · External reference
Clinical pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-54175446, a brain permeable P2X7 antagonist, in a randomised single-ascending dose study in healthy participants
10.1177/0269881118800067 · 2018 · External reference
Characterization of the central nervous system penetrant and selective purine P2X7 receptor antagonist JNJ-54175446 in patients with major depressive disorder
10.1038/s41398-023-02557-5 · 2023 · External reference
Pharmacology of a novel central nervous system-penetrant P2X7 antagonist JNJ-42253432
10.1124/jpet.114.218487 · 2014 · External reference
A dipolar cycloaddition reaction to access 6-methyl-4,5,6,7-tetrahydro-1H-[1,2,3]triazolo[4,5-c]pyridines enables the discovery synthesis and preclinical profiling of a P2X7 antagonist clinical candidate
10.1021/acs.jmedchem.7b01279 · 2018 · External reference
Characterisation of the pharmacodynamic effects of the P2X7 receptor antagonist JNJ-54175446 using an oral dexamphetamine challenge model in healthy males in a randomised, double-blind, placebo-controlled, multiple ascending dose trial
10.1177/0269881120914206 · 2020 · External reference
Mammalian P2X7 receptor pharmacology: Comparison of recombinant mouse, rat and human P2X7 receptors
10.1111/j.1476-5381.2009.00233.x · 2009 · External reference
Direct labelling of the human P2X7 receptor and identification of positive and negative cooperativity of binding
10.1038/sj.bjp.0707196 · 2007 · External reference
Transcriptomic analysis of purified human cortical microglia reveals age-associated changes
10.1038/nn.4597 · 2017 · External reference
An environment-dependent transcriptional network specifies human microglia identity
10.1126/science.aal3222 · 2017 · External reference
Isolation and culture of microglia
10.1002/cpim.70 · 2019 · External reference
Diverse requirements for microglial survival, specification, and function revealed by defined-medium cultures
10.1016/j.neuron.2017.04.043 · 2017 · External reference
Microglia change from a reactive to an age-like phenotype with the time in culture
10.3389/fncel.2014.00152 · 2014 · External reference
A concern on comparing ‘apples’ and ‘oranges’ when differences between microglia used in human and rodent studies go far, far beyond simply species: Comment on Smith and Dragunow
10.1016/j.tins.2014.02.004 · 2014 · External reference
Efficient derivation of microglia-like cells from human pluripotent stem cells
10.1038/nm.4189 · 2016 · External reference
iPSC-derived human microglia-like cells to study neurological diseases
10.1016/j.neuron.2017.03.042 · 2017 · External reference
Characterization of human monocyte-derived microglia-like cells
10.1002/glia.20372 · 2006 · External reference
Patient-specific monocyte-derived microglia as a screening tool for neurodegenerative diseases
10.4103/1673-5374.355740 · 2023 · External reference
A human microglia-like cellular model for assessing the effects of neurodegenerative disease gene variants
10.1126/scitranslmed.aai7635 · 2017 · External reference
Human monocyte-derived microglia-like cell models: A review of the benefits, limitations and recommendations
10.1016/j.bbi.2022.09.015 · 2023 · External reference
Validation of induced microglia-like cells (iMG cells) for future studies of brain diseases
10.3389/fncel.2021.629279 · 2021 · External reference
Direct induction of ramified microglia-like cells from human monocytes: Dynamic microglial dysfunction in Nasu-Hakola disease
10.1038/srep04957 · 2014 · External reference
Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning
10.1038/s41593-018-0334-7 · 2019 · External reference
Transcriptomic and functional analysis of Aβ1–42 oligomer-stimulated human monocyte-derived microglia-like cells
10.1016/j.bbi.2021.12.001 · 2022 · External reference
A robust approach to differentiate human monocyte-derived microglia from peripheral blood mononuclear cells
10.1016/j.xpro.2022.101747 · 2022 · External reference
A novel in vitro human microglia model: Characterization of human monocyte-derived microglia
10.1016/j.jneumeth.2012.05.025 · 2012 · External reference
Seizure suppression and neuroprotection by targeting the purinergic P2X7 receptor during status epilepticus in mice
10.1096/fj.11-196089 · 2012 · External reference
A potential therapeutic role for P2X7 receptor (P2X7R) antagonists in the treatment of inflammatory diseases
10.1517/13543784.2011.578068 · 2011 · External reference
Safety and efficacy of an oral inhibitor of the purinergic receptor P2X7 in adult patients with moderately to severely active Crohn’s disease: A randomized placebo-controlled, double-blind, phase IIa study
2015 · External reference
Targeting the P2X7 receptor in rheumatoid arthritis: Biological rationale for P2X7 antagonism
2014 · External reference
Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine
10.1136/annrheumdis-2011-143578 · 2012 · External reference
The evolution of P2X7 antagonists with a focus on CNS indications
10.1016/j.bmcl.2016.06.048 · 2016 · External reference
Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states
10.1038/sj.bjp.0707265 · 2007 · External reference
[3H]A-804598 ([3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for P2X7 receptors
10.1016/j.neuropharm.2008.06.012 · 2009 · External reference
Synthesis, SAR, and pharmacological characterization of brain penetrant P2X7 receptor antagonists
10.1021/acsmedchemlett.5b00089 · 2015 · External reference
Anti-seizure effects of JNJ-54175446 in the intra-amygdala kainic acid model of drug-resistant temporal lobe epilepsy in mice
10.3389/fphar.2023.1308478 · 2024 · External reference
Microglia dynamics in adolescent traumatic brain injury
10.1186/s12974-020-01994-z · 2020 · External reference
Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response
10.1186/s12974-021-02197-w · 2021 · External reference
Depression following a traumatic brain injury: Uncovering cytokine dysregulation as a pathogenic mechanism
10.4103/1673-5374.238604 · 2018 · External reference
Microglia research in the 100th year since its discovery
10.1007/s12264-020-00477-8 · 2020 · External reference
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
10.1038/nm.3806 · 2015 · External reference
MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition
10.1038/s41589-019-0277-7 · 2019 · External reference
(S)-1-((S)-2-{[1-(4-Amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1β and IL-18
10.1124/jpet.106.111344 · 2007 · External reference
Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase
10.1084/jem.174.4.821 · 1991 · External reference
Human mast cell chymase cleaves pro-IL-18 and generates a novel and biologically active IL-18 fragment
10.4049/jimmunol.177.12.8315 · 2006 · External reference
Stimulation of toll-like receptor 3 and 4 induces interleukin-1β maturation by caspase-8
10.1084/jem.20071632 · 2008 · External reference
A RIPK3–caspase 8 complex mediates atypical pro-IL-1β processing
10.4049/jimmunol.1402167 · 2015 · External reference
Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation
10.1016/j.immuni.2012.01.012 · 2012 · External reference
P2X7R antagonism suppresses long-lasting brain hyperexcitability following traumatic brain injury in mice
10.7150/thno.97254 · 2025 · External reference
Cerebrospinal fluid and microdialysis cytokines in severe traumatic brain injury: A scoping systematic review
10.3389/fneur.2017.00331 · 2017 · External reference
Brain injury induced by intracerebral injection of interleukin-1beta and tumor necrosis factor-alpha in the neonatal rat
10.1203/01.pdr.0000134249.92944.14 · 2004 · External reference
Interleukin-1 causes CNS inflammatory cytokine expression via endothelia-microglia bi-cellular signaling
10.1016/j.bbi.2019.06.026 · 2019 · External reference
Interleukin-1beta plays a role in the activation of peripheral leukocytes after blood-brain barrier rupture in the course of subarachnoid hemorrhage
10.2174/156720210790820226 · 2010 · External reference
Hypoxia-induced changes in tight junction permeability of brain capillary endothelial cells are associated with IL-1beta and nitric oxide
10.1016/j.nbd.2004.08.001 · 2004 · External reference
Cytokines, oxidative stress and cellular markers of inflammation in schizophrenia
10.1007/7854_2018_88 · 2020 · External reference
Cytokine function in medication-naive first episode psychosis: A systematic review and meta-analysis
10.1016/j.schres.2014.03.005 · 2014 · External reference
P2x7 deficiency suppresses development of experimental autoimmune encephalomyelitis
10.1186/1742-2094-5-33 · 2008 · External reference
P2X7 receptor antagonism as a potential therapy in amyotrophic lateral sclerosis
10.3389/fnmol.2020.00093 · 2020 · External reference
Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain
10.1016/j.pain.2005.01.002 · 2005 · External reference
P2X receptors as drug targets
10.1124/mol.112.083758 · 2013 · External reference