{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:22:11Z","timestamp":1792182131662,"version":"4.4.0"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    Traumatic brain injuries (TBI) caused by physical impact to the brain can adversely impact the welfare and well-being of the affected individuals. One of the leading causes of mortality and dysfunction in the world, TBI is a major public health problem facing the human community. Drugs that target GABAergic neurotransmission are commonly used for sedation in clinical TBI yet their potential to cause neuroprotection is unclear. In this paper, I have performed a rigorous literature review of the neuroprotective effects of drugs that increase GABAergic currents based on the results reported in preclinical literature. The drugs covered in this review include the following: propofol, benzodiazepines, barbiturates, isoflurane, and other drugs that are agonists of GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors. A careful review of numerous preclinical studies reveals that these drugs fail to produce any neuroprotection after a primary impact to the brain. In numerous circumstances, they could be detrimental to neuroprotection by increasing the size of the contusional brain tissue and by severely interfering with behavioral and functional recovery. Therefore, anesthetic agents that work by enhancing the effect of neurotransmitter GABA should be administered with caution of TBI patients until a clear and concrete picture of their neuroprotective efficacy emerges in the clinical literature.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2023.1109406","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T23:56:56Z","timestamp":1675295816000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Are GABAergic drugs beneficial in providing neuroprotection after traumatic brain injuries? A comprehensive literature review of preclinical studies"],"prefix":"10.3389","volume":"14","author":[{"given":"Shyam Kumar","family":"Sudhakar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1179\/016164102101199503","article-title":"Epidemiology of traumatic brain injuries: Indian scenario","volume":"24","author":"Gururaj","year":"2002","journal-title":"Neurol Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1097\/00001199-200609000-00001","article-title":"The epidemiology and impact of traumatic brain injury a brief overview","volume":"21","author":"Langlois","year":"2006","journal-title":"J Head Trauma Rehabil."},{"key":"B3","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/S1474-4422(08)70164-9","article-title":"Moderate and severe traumatic brain injury in adults","volume":"7","author":"Maas","year":"2008","journal-title":"Lancet Neurol."},{"key":"B4","first-page":"3","article-title":"After traumatic brain injury","volume":"156","author":"Shoumitro","year":"1999","journal-title":"AM J Psychiatry."},{"key":"B5","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1136\/jnnp.49.7.764","article-title":"The five year outcome of severe blunt head injury: a relative's view","volume":"49","author":"Brooks","year":"1986","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B6","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1080\/0269905001209161","article-title":"Axis II psychopathology in individuals with traumatic brain injury","volume":"13","author":"Hibbard","year":"2000","journal-title":"Brain Injury."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1093\/bja\/aem131","article-title":"Pathophysiology of traumatic brain injury","volume":"99","author":"Werner","year":"2007","journal-title":"Br J Anaesth."},{"key":"B8","doi-asserted-by":"publisher","first-page":"309","DOI":"10.3390\/ijms15010309","article-title":"Traumatic brain injury pathophysiology and treatments: early, intermediate, and late phases post-injury","volume":"15","author":"Algattas","year":"2013","journal-title":"Int J Mol Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.injury.2012.01.011","article-title":"Redefining the golden hour for severe head injury in an urban setting: the effect of prehospital arrival times on patient outcomes","volume":"44","author":"Dinh","year":"2013","journal-title":"Injury."},{"key":"B10","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1097\/00005373-199302000-00014","article-title":"Impact of on-site care, prehospital time, and level of in-hospital care on survival in severely injured patients","volume":"34","author":"Sampalis","year":"1993","journal-title":"J Trauma."},{"key":"B11","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1517\/14728210902769601","article-title":"Emerging treatments for traumatic brain injury","volume":"14","author":"Xiong","year":"2009","journal-title":"Expert Opin Emerg Drugs."},{"key":"B12","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1089\/neu.2008.0586","article-title":"Classification of traumatic brain injury for targeted therapies","volume":"25","author":"Saatman","year":"2008","journal-title":"J Neurotrauma."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.cjtee.2016.01.001","article-title":"Traumatic brain injury: changing concepts and approaches","volume":"19","author":"Maas","year":"2016","journal-title":"Chin J Traumatol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/637171","article-title":"Sedation in traumatic brain injury","volume":"2012","author":"Flower","year":"2012","journal-title":"Emerg Med Int."},{"key":"B15","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1476-4431.2006.00194.x","article-title":"Anesthetic management of the head trauma patient","volume":"17","author":"Armitage-Chan","year":"2007","journal-title":"J Vet Emerg Crit Care."},{"key":"B16","article-title":"Sedation in TBI patients","author":"Peluso","year":"2019","journal-title":"Traumatic Brain Injury"},{"key":"B17","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1097\/00003246-200201000-00020","article-title":"Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult","volume":"30","author":"Jacobi","year":"2002","journal-title":"Crit Care Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/b978-0-323-54456-6.00011-6","article-title":"Pharmacologic management of the patient with traumatic brain injury","author":"Ripley","year":"2019","journal-title":"Rehabilitation After Traumatic Brain Injury"},{"key":"B19","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1089\/neu.2006.23.97","article-title":"Comparison of seven anesthetic agents on outcome after experimental traumatic brain injury in adult, male rats","volume":"23","author":"Statler","year":"2006","journal-title":"J Neurotrauma."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e19948","DOI":"10.1371\/journal.pone.0019948","article-title":"Influence of a brief episode of anesthesia during the induction of experimental brain trauma on secondary brain damage and inflammation","volume":"6","author":"Luh","year":"2011","journal-title":"PLoS ONE."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1089\/neu.2000.17.1179","article-title":"Isoflurane improves long-term neurologic outcome versus fentanyl after traumatic brain injury in rats","volume":"17","author":"Statler","year":"2000","journal-title":"J Neurotrauma."},{"key":"B22","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/0006-8993(86)90261-1","article-title":"Recovery of function after brain damage : severe and chronic disruption by diazepam","volume":"379","author":"Schallert","year":"1986","journal-title":"Brain Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/0006-8993(94)91451-6","article-title":"Disruption of behavioral recovery by the anti-convulsant phenobarbital","volume":"635","author":"Hernandez","year":"1994","journal-title":"Brain Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1136\/jnnp.58.6.753","article-title":"Prescribing of potentially harmful drugs to patients admitted to hospital after head injury","volume":"58","author":"Goldstein","year":"1995","journal-title":"J NeurolNeurosurgPsychiatry."},{"key":"B25","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1126\/science.aag2590","article-title":"How neuroinflammation contributes to neurodegeneration","volume":"353","author":"Ransohoff","year":"2016","journal-title":"Science"},{"key":"B26","doi-asserted-by":"crossref","first-page":"526","DOI":"10.55782\/ane-2008-1720","article-title":"Pro-inflammatory cytokine TNF-\u03b1 as a neuroprotective agent in the brain","volume":"68","author":"Izabela","year":"2008","journal-title":"Acta Neurobiol Exp"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3963","DOI":"10.4049\/jimmunol.163.7.3963","article-title":"Inflammatory Cytokines IL-1, IL-1, IL-6, and TNF-impart neuroprotection to an excitotoxin through distinct pathways 1","volume":"163","author":"Carlson","year":"1999","journal-title":"J Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1097\/00075198-200204000-00002","article-title":"Inflammatory response in acute traumatic brain injury: a double-edged sword","volume":"8","author":"Morganti-Kossmann","year":"2002","journal-title":"Curr Opin Crit Care."},{"key":"B29","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/nrneurol.2017.13","article-title":"The far-reaching scope of neuroinflammation after traumatic brain injury","volume":"13","author":"Simon","year":"2017","journal-title":"Nat Rev Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1124\/mol.64.2.373","article-title":"Isoflurane and propofol inhibit voltage-gated sodium channels in isolated rat neurohypophysial nerve terminals","volume":"64","author":"Ouyang","year":"2003","journal-title":"Mol Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1097\/CCM.0b013e3182a639fd","article-title":"Propofol impairs neurogenesis and neurologic recovery and increases mortality rate in adult rats after traumatic brain injury","volume":"42","author":"Thal","year":"2014","journal-title":"Crit Care Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e70","DOI":"10.1097\/CCM.0000000000001284","article-title":"Posttraumatic propofol neurotoxicity is mediated via the pro-brain-derived neurotrophic factor-p75 neurotrophin receptor pathway in adult mice","volume":"44","author":"Sebastiani","year":"2016","journal-title":"Crit Care Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1213\/01.ane.0000247803.30582.2d","article-title":"The effect of electroencephalogram-targeted high- and low-dose propofol infusion on histopathological damage after traumatic brain injury in the rat","volume":"103","author":"Ebersp\u00e4cher","year":"2006","journal-title":"Anesth Analg."},{"key":"B34","doi-asserted-by":"publisher","first-page":"253","DOI":"10.2478\/abm-2021-0032","article-title":"Propofol effects in rodent models of traumatic brain injury: a systematic review","volume":"15","author":"Firdaus","year":"2021","journal-title":"Asian Biomed."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1097\/ALN.0000000000000020","article-title":"Propofol limits microglial activation after experimental brain trauma through inhibition of nicotinamide adenine dinucleotide phosphate oxidase","volume":"119","author":"Luo","year":"2013","journal-title":"Anesthesiology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s12013-013-9549-0","article-title":"Propofol administration modulates AQP-4 expression and brain edema after traumatic brain injury","volume":"67","author":"Ding","year":"2013","journal-title":"Cell Biochem Biophys."},{"key":"B37","doi-asserted-by":"publisher","first-page":"919","DOI":"10.4103\/0366-6999.154298","article-title":"Propofol ameliorates calpain-induced collapsin response mediator protein-2 proteolysis in traumatic brain injury in rats","volume":"128","author":"Yu","year":"2015","journal-title":"Chin Med J."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.1089\/neu.2018.6162","article-title":"Diazepam inhibits post-traumatic neurogenesis and blocks aberrant dendritic development","volume":"36","author":"Villasana","year":"2019","journal-title":"J Neurotrauma."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12871-022-01592-x","article-title":"Posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury","volume":"22","author":"Sebastiani","year":"2022","journal-title":"BMC Anesthesiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"8079","DOI":"10.3892\/mmr.2018.8898","article-title":"Neuroprotective effects of dexmedetomidine on traumatic brain injury: involvement of neuronal apoptosis and HSP70 expression","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol Med Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0166-4328(05)80306-7","article-title":"Subcortical deterioration after cortical damage: effects of diazepam and relation to recovery of function","volume":"51","author":"Jones","year":"1992","journal-title":"Behav Brain Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/S0006-8993(00)02055-2","article-title":"Positive and negative modulation of the GABA(A) receptor and outcome after traumatic brain injury in rats","volume":"861","author":"O'Dell","year":"2000","journal-title":"Brain Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.brainres.2005.12.106","article-title":"Isoflurane exerts neuroprotective actions at or near the time of severe traumatic brain injury","volume":"1076","author":"Statler","year":"2006","journal-title":"Brain Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1159\/000448089","article-title":"Long-term anesthetic-dependent hypoactivity after repetitive mild traumatic brain injuries in adolescent mice","volume":"38","author":"Semple","year":"2016","journal-title":"Dev Neurosci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1007\/s00701-004-0281-9","article-title":"Differential effects of prolonged isoflurane anesthesia on plasma, extracellular, and CSF glutamate, neuronal activity, 125I-Mk801 NMDA receptor binding, and brain edema in traumatic brain-injured rats","volume":"146","author":"Stover","year":"2004","journal-title":"Acta Neurochir."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e50752","DOI":"10.1371\/journal.pone.0050752","article-title":"Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury","volume":"7","author":"Thal","year":"2012","journal-title":"PLoS ONE"},{"key":"B47","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/978-3-7091-0956-4_74","article-title":"Influence of isoflurane on neuronal death and outcome in a rat model of traumatic brain injury","volume":"114","author":"Hertle","year":"2012","journal-title":"Acta Neurochir Supp"},{"key":"B48","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1089\/089771504774129847","article-title":"Differential effects of the anticonvulsant topiramate on neurobehavioral and histological outcomes following traumatic brain injury in rats","volume":"21","author":"Hoover","year":"2004","journal-title":"J Neurotrauma."},{"key":"B49","first-page":"35","article-title":"Impact of the novel anti-convulsant vigabatrin on functional recovery following brain lesion","volume":"14","author":"Wallace","year":"1999","journal-title":"Restor Neurol Neurosci."},{"key":"B50","first-page":"214","article-title":"Benzodiazepine pharmacology and central nervous system-mediated effects","volume":"13","author":"Griffin","year":"2013","journal-title":"Ochsner J."},{"key":"B51","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/0006-8993(89)90943-8","article-title":"Co-administration of Ro 15-1788 prevents diazepam-induced retardation of recovery of function","volume":"487","author":"Hernandez","year":"1989","journal-title":"Brain Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1089\/neu.2009.1142","article-title":"Flumazenil administration attenuates cognitive impairment in immature rats after controlled cortical impact","volume":"27","author":"Ochalski","year":"2010","journal-title":"J Neurotrauma."},{"key":"B53","article-title":"Barbiturates","author":"Skibiski","year":"2022"},{"key":"B54","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1097\/00000542-199504000-00024","article-title":"Isoflurane reduces ischemia-induced glutamate release in rats subjected to forebrain ischemia","volume":"82","author":"Patel","year":"1995","journal-title":"Anesthesiology."},{"key":"B55","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1124\/jpet.104.074609","article-title":"Depression by isoflurane of the action potential and underlying voltage-gated ion currents in isolated rat neurohypophysial nerve terminals","volume":"312","author":"Ouyang","year":"2005","journal-title":"J Pharmacol Exp Ther"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1097\/00000542-199412000-00022","article-title":"Effects of lsoflurane and hypothermia on glutamate receptor-mediated calcium influx in brain slices","volume":"81","author":"Bickler","year":"1994","journal-title":"Anesthesiology."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1097\/00000542-199812000-00026","article-title":"Local cerebral blood flow, local cerebral glucose utilization, and flow-metabolism coupling during sevoflurane versus isoflurane anesthesia in rats","volume":"89","author":"Lenz","year":"1998","journal-title":"Anesthesiology."},{"key":"B58","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1006\/phrs.1997.0124","article-title":"A pharmacological and clinical review on topiramate, a new antiepileptic drug","volume":"35","author":"Perucca","year":"1997","journal-title":"Pharmacol Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/0006-8993(86)90457-9","volume":"362","author":"Brailowsky","year":"1986","journal-title":"Brain Res."},{"key":"B60","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3233\/RNN-1990-1503","article-title":"Long-term impairment of behavioral recovery from cortical damage can be produced by short-term GABA-agonist infusion into adjacent cortex","volume":"1","author":"Hernandez","year":"1990","journal-title":"Restor Neurol Neurosci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/0014-4886(88)90226-9","article-title":"Seizures and recovery from experimental brain damage","volume":"102","author":"Hernandez","year":"1988","journal-title":"Exp Neurol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"107","DOI":"10.2165\/00002018-200427020-00003","article-title":"Comparative tolerability of sedative agents in head-injured adults","volume":"27","author":"Urwin","year":"2004","journal-title":"Drug Saf."},{"key":"B63","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1097\/00003246-199502000-00014","article-title":"Comparison of propofol and midazolam for sedation in intensive care unit patients","volume":"23","author":"Ronan","year":"1995","journal-title":"Crit Care Med"},{"key":"B64","doi-asserted-by":"publisher","first-page":"i44","DOI":"10.1093\/bja\/aex328","article-title":"Thiopental to desflurane-an anaesthetic journey. Where are we going next?","volume":"119","author":"Sneyd","year":"2017","journal-title":"Br J Anaesth."},{"key":"B65","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1111\/pan.12083","article-title":"Thiopentone and its challengers","volume":"23","author":"Brown","year":"2013","journal-title":"Paediatr Anaesth."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2007.9985","article-title":"XI. Anesthetics, analgesics, and sedatives","author":"Bratton","year":"2007","journal-title":"J Neurotrauma"},{"key":"B67","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD000033","article-title":"Barbiturates for acute traumatic brain injury","author":"Roberts","year":"1999","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/cc6999","article-title":"Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial","volume":"12","author":"P\u00e9rez-B\u00e1rcena","year":"2008","journal-title":"Crit Care."},{"key":"B69","doi-asserted-by":"publisher","first-page":"e0268013","DOI":"10.1371\/journal.pone.0268013","article-title":"Early use of barbiturates is associated with increased mortality in traumatic brain injury patients from a propensity score-based analysis of a prospective cohort","volume":"17","author":"L\u00e9ger","year":"2022","journal-title":"PLoS ONE."},{"key":"B70","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.pneurobio.2014.01.001","article-title":"Neuroprotective gases - fantasy or reality for clinical use?","volume":"115","author":"Deng","year":"2014","journal-title":"Prog Neurobiol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"2797","DOI":"10.1097\/CCM.0b013e31825b8bc6","article-title":"Inhalation versus endovenous sedation in subarachnoid hemorrhage patients: effects on regional cerebral blood flow","volume":"40","author":"Villa","year":"2012","journal-title":"Crit Care Med."},{"key":"B72","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1007\/BF03018431","article-title":"Propofol offers no advantage over isoflurane anes-thesia for cerebral protection during cardiopul-monary bypass: a preliminary study of S-100\u00dfprotein levels","volume":"51","author":"Kanbak","year":"2004","journal-title":"Can J Anaesth"},{"key":"B73","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1097\/00000542-198709000-00010","article-title":"Frank isoflurane when compared to enflurane and halothane decreases the frequency of cerebral ischemia during carotid endarterectomy","volume":"67","author":"Michenfelder","year":"1987","journal-title":"Anesthesiology."},{"key":"B74","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1113\/jphysiol.1989.sp017762","article-title":"Giant synaptic potentials in immature rat CA3 hippocampal neurones","volume":"416","author":"Ben-Ari","year":"1989","journal-title":"J Physiol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1177\/1073858412438697","article-title":"The GABA excitatory\/inhibitory shift in brain maturation and neurological disorders","volume":"18","author":"Ben-Ari","year":"2012","journal-title":"Neuroscientist."},{"key":"B76","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1002\/(SICI)1097-4695(19971120)33:6<781::AID-NEU6>3.0.CO;2-5","article-title":"Expression of the Na \u2013 K \u2013 2Cl cotransporter is developmentally regulated in postnatal rat brains : a possible mechanism underlying GABA's excitatory role in immature brain","volume":"33","author":"Plotkin","year":"1997","journal-title":"J Neurobiol"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms8750","article-title":"depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo","volume":"6","author":"Kirmse","year":"2015","journal-title":"Nat Commun."},{"key":"B78","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/S0166-2236(03)00068-7","article-title":"Cation-chloride co-transporters in neuronal communication, development and trauma","volume":"26","author":"Payne","year":"2003","journal-title":"Trends Neurosci."},{"key":"B79","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/(SICI)1097-4695(19990615)39:4<558::AID-NEU9>3.0.CO;2-5","article-title":"Developmental regulation of the neuronal-specific isoform of K-Cl cotransporter KCC2 in postnatal rat brains","volume":"39","author":"Lu","year":"1999","journal-title":"J Neurobiol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.neuint.2016.02.002","article-title":"Inhibition of Na+-K+-2Cl- cotransporter-1 attenuates traumatic brain injury-induced neuronal apoptosis via regulation of erk signaling","volume":"94","author":"Hui","year":"2016","journal-title":"Neurochem Int."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1007\/s00429-016-1292-z","article-title":"NKCC1 up-regulation contributes to early post-traumatic seizures and increased post-traumatic seizure susceptibility","volume":"222","author":"Wang","year":"2017","journal-title":"Brain Struct Funct."},{"key":"B82","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1097\/CCM.0B013E31816590C4","article-title":"NKCC1-mediated traumatic brain injury-induced brain edema and neuron death via raf\/mek\/mapk cascade","volume":"36","author":"Lu","year":"2008","journal-title":"Crit Care Med."},{"key":"B83","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.nbd.2006.09.002","article-title":"Brain injury impairs dentate gyrus inhibitory efficacy","volume":"25","author":"Bonislawski","year":"2007","journal-title":"Neurobiol Dis."},{"key":"B84","doi-asserted-by":"publisher","first-page":"4283","DOI":"10.1523\/JNEUROSCI.16-13-04283.1996","article-title":"Excitatory actions of GABA after neuronal trauma","volume":"16","author":"Pol van den","year":"1996","journal-title":"J Neurosci"},{"key":"B85","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.ejphar.2006.07.048","article-title":"Inhibition of the Na+-K+-2Cl\u2013cotransporter in choroid plexus attenuates traumatic brain injury-induced brain edema and neuronal damage","volume":"548","author":"Lu","year":"2006","journal-title":"Eur J Pharmacol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.tins.2017.07.001","article-title":"NKCC1 chloride importer antagonists attenuate many neurological and psychiatric disorders","volume":"40","author":"Ben-Ari","year":"2017","journal-title":"Trends Neurosci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1179\/016164107X204738","article-title":"Bumetanide administration attenuated traumatic brain injury through IL-1 overexpression","volume":"29","author":"Lu","year":"2007","journal-title":"Neurol Res."},{"key":"B88","doi-asserted-by":"publisher","first-page":"611","DOI":"10.3171\/2009.11.JNS081052","article-title":"Molecular mechanisms of microvascular failure in CNS injury - synergistic roles of NKCC1 and SUR1\/TRPM4","volume":"113","author":"Kahle","year":"2010","journal-title":"J Neurosurg."},{"key":"B89","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/neu.2018.6065","article-title":"Biophysical modeling suggests optimal drug combinations for improving the efficacy of GABA agonists after traumatic brain injuries","volume":"36","author":"Sudhakar","year":"2019","journal-title":"J Neurotrauma."},{"key":"B90","unstructured":"Biophysical modeling reveals efficacious drug combinations for improved neuroprotection immediately after traumatic brain injury SudhakarSK ChoiTJ HetrickV AhmedOJ Soc Neurosci Abstracts.2018"},{"key":"B91","doi-asserted-by":"publisher","first-page":"9866","DOI":"10.1523\/JNEUROSCI.2761-07.2007","article-title":"Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy","volume":"27","author":"Huberfeld","year":"2007","journal-title":"J Neurosci"},{"key":"B92","doi-asserted-by":"publisher","first-page":"E1618","DOI":"10.1073\/pnas.1716871115","article-title":"Restoring GABAergic inhibition rescues memory deficits in a Huntington's disease mouse model","volume":"115","author":"Dargaei","year":"2018","journal-title":"Proc Nat Acad Sci."},{"key":"B93","doi-asserted-by":"publisher","first-page":"8465","DOI":"10.1073\/pnas.0602979103","article-title":"Anomalous levels of Cl- transporters in the hippocampal subiculum from temporal lobe epilepsy patients make GABA excitatory","volume":"103","author":"Palma","year":"2006","journal-title":"Proc Nat Acad Sci."},{"key":"B94","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1126\/science.7638623","article-title":"Ionic mechanisms of neuronal excitation by inhibitory GABA(A) receptors","volume":"269","author":"Staley","year":"1995","journal-title":"Science."},{"key":"B95","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.eplepsyres.2008.09.008","article-title":"Bicarbonate contributes to GABAA receptor-mediated neuronal excitation in surgically resected human hypothalamic hamartomas","volume":"83","author":"Kim","year":"2009","journal-title":"Epilepsy Res."},{"key":"B96","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1113\/jphysiol.1993.sp019634","article-title":"The role of bicarbonate in GABAA receptor-mediated IPSPs of rat neocortical neurones","volume":"464","author":"Kaila","year":"1993","journal-title":"J Physiol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1111\/j.1469-7793.1999.0693n.x","article-title":"Modulation of mammalian dendritic GABA(A) receptor function by the kinetics of Cl-and HCO3-transport","volume":"519","author":"Staley","year":"1999","journal-title":"J Physiol."},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1186\/1423-0127-17-38","article-title":"Traumatic brain injury and the effects of diazepam, diltiazem, and MK-801 on GABA-A receptor subunit expression in rat hippocampus","author":"Gibson","year":"2010","journal-title":"J Biomed Sci"},{"key":"B99","doi-asserted-by":"publisher","first-page":"2548","DOI":"10.1089\/neu.2012.2483","article-title":"GABAA receptor regulation after experimental traumatic brain injury","volume":"29","author":"Raible","year":"2012","journal-title":"J Neurotrauma."},{"key":"B100","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1089\/089771504322972059","article-title":"Potentiation of GABA(A) currents after mechanical injury of cortical neurons","volume":"21","author":"Kao","year":"2004","journal-title":"J Neurotrauma"},{"key":"B101","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1046\/j.1471-4159.2001.00428.x","article-title":"Changes in mACh, NMDA and GABAA receptor binding after lateral fluid-percussion injury: In vitro autoradiography of rat brain frozen sections","volume":"78","author":"Sihver","year":"2001","journal-title":"J Neurochem."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.4103\/1673-5374.255957","article-title":"Remodeling dendritic spines for treatment of traumatic brain injury","volume":"14","author":"Xiong","year":"2019","journal-title":"Neural Regen Res."},{"key":"B103","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1080\/08998280.2001.11927725","article-title":"Dexmedetomidine: a novel sedative-analgesic agent","volume":"14","author":"Gertler","year":"2001","journal-title":"Proc (Bayl Univ Med Cent)"},{"key":"B104","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3892\/etm.2020.9436","article-title":"Dexmedetomidine inhibits the PSD95-NMDA receptor interaction to promote functional recovery following traumatic brain injury","volume":"20","author":"Zhao","year":"2020","journal-title":"Exp Ther Med."},{"key":"B105","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.biopha.2017.08.125","article-title":"Dexmedetomidine exerts neuroprotective effect via the activation of the PI3K\/Akt\/mTOR signaling pathway in rats with traumatic brain injury","volume":"95","author":"Shen","year":"2017","journal-title":"Biomed Pharmacother."},{"key":"B106","doi-asserted-by":"publisher","first-page":"819","DOI":"10.4103\/1673-5374.232529","article-title":"Dexmedetomidine attenuates traumatic brain injury: action pathway and mechanisms","volume":"13","author":"Wang","year":"2018","journal-title":"Neural Regen Res."},{"key":"B107","doi-asserted-by":"publisher","first-page":"4935","DOI":"10.1038\/s41598-018-23003-3","article-title":"Neuroprotective effect of dexmedetomidine in a murine model of traumatic brain injury","volume":"8","author":"Wu","year":"2018","journal-title":"Sci Rep"},{"key":"B108","doi-asserted-by":"publisher","first-page":"46682","DOI":"10.1016\/j.brainres.2020.146682","article-title":"Dexmedetomidine attenuates endoplasmic reticulum stress-induced apoptosis and improves neuronal function after traumatic brain injury in mice","volume":"1732","author":"Sun","year":"2020","journal-title":"Brain Res"},{"key":"B109","doi-asserted-by":"publisher","first-page":"661","DOI":"10.3892\/mmr.2021.12300","article-title":"Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS\/Nrf2 signaling pathway","volume":"24","author":"Feng","year":"2021","journal-title":"Mol Med Rep"},{"key":"B110","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1097\/00006123-199908000-00001","article-title":"Current status of neuroprotection trials for traumatic brain injury: lessons from animal models and clinical studies","volume":"45","author":"Bullock","year":"1999","journal-title":"Neurosurgery"},{"key":"B111","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/S0079-6123(09)17515-5","article-title":"Progesterone as a neuroprotective factor in traumatic and ischemic brain injury","volume":"175","author":"Sayeed","year":"2009","journal-title":"Prog Brain Res."},{"key":"B112","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.3109\/02699052.2015.1065344","article-title":"Embracing failure: What the phase III progesterone studies can teach about TBI clinical trials","volume":"29","author":"Stein","year":"2015","journal-title":"Brain Inj."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1109406\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T20:45:44Z","timestamp":1701809144000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1109406\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":112,"alternative-id":["10.3389\/fneur.2023.1109406"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1109406","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]},"article-number":"1109406"}}