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Volume 24, Issue 1
  • ISSN: 1871-5273
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Abstract

Traumatic Brain Injury (TBI) is attributed to a forceful impact on the brain caused by sharp, penetrating bodies, like bullets and any sharp object. Some popular instances like falls, traffic accidents, physical assaults, and athletic injuries frequently cause TBI. TBI is the primary cause of both mortality and disability among young children and adults. Several individuals experience psychiatric problems, including cognitive dysfunction, depression, post-traumatic stress disorder, and anxiety, after primary injury. Behavioral changes post TBI include cognitive deficits and emotional instability (anxiety, depression, and post-traumatic stress disorder). These alterations are linked to neuroinflammatory processes. On the other hand, the direct impact mitigates inflammation insult by the release of pro-inflammatory cytokines, namely IL-1β, IL-6, and TNF-α, exacerbating neuronal injury and contributing to neurodegeneration. During the excitotoxic phase, activation of glutamate subunits like NMDA enhances the influx of Ca2+ and leads to mitochondrial metabolic impairment and calpain-mediated cytoskeletal disassembly. TBI pathological insult is also linked to transcriptional response suppression Nrf-2, which plays a critical role against TBI-induced oxidative stress. Activation of NRF-2 enhances the expression of anti-oxidant enzymes, providing neuroprotection. A possible explanation for the elevated levels of NO is that the stimulation of NMDA receptors by glutamate leads to the influx of calcium in the postsynaptic region, activating NOS's constitutive isoforms.

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2024-07-30
2024-11-22

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References

  1. RanaA. SinghS. DeshmukhR. KumarA. Pharmacological potential of tocopherol and doxycycline against traumatic brain injury-induced cognitive/motor impairment in rats.Brain Inj.20203481039105010.1080/02699052.2020.177250832493074
     [Google Scholar]
  2. IaccarinoC. CarrettaA. NicolosiF. MorselliC. Epidemiology of severe traumatic brain injury.J. Neurosurg. Sci.201862553554110.23736/S0390‑5616.18.04532‑030182649
     [Google Scholar]
  3. SieboldL. ObenausA. GoyalR. Criteria to define mild, moderate, and severe traumatic brain injury in the mouse controlled cortical impact model.Exp. Neurol.2018310485710.1016/j.expneurol.2018.07.00430017882
     [Google Scholar]
  4. WernerC. EngelhardK. Pathophysiology of traumatic brain injury.Br. J. Anaesth.20079914910.1093/bja/aem13117573392
     [Google Scholar]
  5. WortzelH.S. ArciniegasD.B. Treatment of post-traumatic cognitive impairments.Curr. Treat. Options Neurol.201214549350810.1007/s11940‑012‑0193‑622865461
     [Google Scholar]
  6. IetswaartM. MildersM. CrawfordJ.R. CurrieD. ScottC.L. Longitudinal aspects of emotion recognition in patients with traumatic brain injury.Neuropsychologia200846114815910.1016/j.neuropsychologia.2007.08.00217915263
     [Google Scholar]
  7. SilverJ.M. McAllisterT.W. ArciniegasD.B. Depression and cognitive complaints following mild traumatic brain injury.Am. J. Psychiatry2009166665366110.1176/appi.ajp.2009.0811167619487401
     [Google Scholar]
  8. LoaneD.J. ByrnesK.R. Role of microglia in neurotrauma.Neurotherapeutics20107436637710.1016/j.nurt.2010.07.00220880501
     [Google Scholar]
  9. RodneyT. OsierN. GillJ. Pro- and anti-inflammatory biomarkers and traumatic brain injury outcomes: A review.Cytokine201811024825610.1016/j.cyto.2018.01.01229396048
     [Google Scholar]
  10. AhmedS.M.U. LuoL. NamaniA. WangX.J. TangX. Nrf2 signaling pathway: Pivotal roles in inflammation.Biochim. Biophys. Acta Mol. Basis Dis.20171863258559710.1016/j.bbadis.2016.11.00527825853
     [Google Scholar]
  11. DorsettC.R. McGuireJ.L. DePasqualeE.A.K. GardnerA.E. FloydC.L. McCullumsmithR.E. Glutamate neurotransmission in rodent models of traumatic brain injury.J. Neurotrauma201734226327210.1089/neu.2015.437327256113
     [Google Scholar]
  12. ZhangL. WangH. ZhouX. MaoL. DingK. HuZ. Role of mitochondrial calcium uniporter‐mediated Ca 2+ and iron accumulation in traumatic brain injury.J. Cell. Mol. Med.20192342995300910.1111/jcmm.1420630756474
     [Google Scholar]
  13. CherianL. HlatkyR. RobertsonC.S. Nitric oxide in traumatic brain injury.Brain Pathol.200414219520110.1111/j.1750‑3639.2004.tb00053.x15193032
     [Google Scholar]
  14. PopescuC. AnghelescuA. DaiaC. OnoseG. Actual data on epidemiological evolution and prevention endeavours regarding traumatic brain injury.J. Med. Life20158327227726351526
     [Google Scholar]
  15. KamalV.K. AgrawalD. PandeyR.M. Epidemiology, clinical characteristics and outcomes of traumatic brain injury: Evidences from integrated level 1 trauma center in India.J. Neurosci. Rural Pract.20167451552510.4103/0976‑3147.18863727695230
     [Google Scholar]
  16. ShekharC. GuptaL. PremsagarI. SinhaM. KishoreJ. An epidemiological study of traumatic brain injury cases in a trauma centre of New Delhi (India).J. Emerg. Trauma Shock20158313113910.4103/0974‑2700.16070026229295
     [Google Scholar]
  17. AgrawalA. MunivenkatappaA. ShuklaD. MenonG. AlogoluR. GalwankarS. KumarS. MomhanP. PalR. RustagiN. Traumatic brain injury related research in India: An overview of published literature.Int. J. Crit. Illn. Inj. Sci.201662656910.4103/2229‑5151.18302527308253
     [Google Scholar]
  18. CorriganJ.D. SelassieA.W. OrmanJ.A.L. The epidemiology of traumatic brain injury.J. Head Trauma Rehabil.2010252728010.1097/HTR.0b013e3181ccc8b420234226
     [Google Scholar]
  19. MajdanM. PlancikovaD. MaasA. PolinderS. FeiginV. TheadomA. RusnakM. BrazinovaA. HaagsmaJ. Years of life lost due to traumatic brain injury in Europe: A cross-sectional analysis of 16 countries.PLoS Med.2017147e100233110.1371/journal.pmed.100233128700588
     [Google Scholar]
  20. GururajG. Epidemiology of traumatic brain injuries: Indian scenario.Neurol. Res.2002241242810.1179/01616410210119950311783750
     [Google Scholar]
  21. Te AoB. TobiasM. AmeratungaS. McPhersonK. TheadomA. DowellA. StarkeyN. JonesK. Barker-ColloS. BrownP. FeiginV. Burden of traumatic brain injury in New Zealand: Incidence, prevalence and disability-adjusted life years.Neuroepidemiology201544425526110.1159/00043104326088707
     [Google Scholar]
  22. BarmanA. ChatterjeeA. BhideR. Cognitive impairment and rehabilitation strategies after traumatic brain injury.Indian J. Psychol. Med.201638317218110.4103/0253‑7176.18308627335510
     [Google Scholar]
  23. DixonC.E. MaX. MarionD.W. Reduced evoked release of acetylcholine in the rodent neocortex following traumatic brain injury.Brain Res.1997749112713010.1016/S0006‑8993(96)01310‑89070636
     [Google Scholar]
  24. LeonardJ.R. MarisD.O. GradyM.S. Fluid percussion injury causes loss of forebrain choline acetyltransferase and nerve growth factor receptor immunoreactive cells in the rat.J. Neurotrauma199411437939210.1089/neu.1994.11.3797837279
     [Google Scholar]
  25. LanY.L. LiS. LouJ.C. MaX.C. ZhangB. The potential roles of dopamine in traumatic brain injury: A preclinical and clinical update.Am. J. Transl. Res.20191152616263131217842
     [Google Scholar]
  26. DhikavV. AnandK.S. Hippocampus in health and disease: An overview.Ann. Indian Acad. Neurol.201215423924610.4103/0972‑2327.10432323349586
     [Google Scholar]
  27. BramlettH. DietrichD. Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats.Acta Neuropathol.2002103660761410.1007/s00401‑001‑0510‑812012093
     [Google Scholar]
  28. ZhangB.L. ChenX. TanT. YangZ. CarlosD. JiangR.C. ZhangJ.N. Traumatic brain injury impairs synaptic plasticity in hippocampus in rats.Chin. Med. J. (Engl.)2011124574074521518569
     [Google Scholar]
  29. GaoX. Deng-BryantY. ChoW. CarricoK.M. HallE.D. ChenJ. Selective death of newborn neurons in hippocampal dentate gyrus following moderate experimental traumatic brain injury.J. Neurosci. Res.200886102258227010.1002/jnr.2167718381764
     [Google Scholar]
  30. LiJ.W. ZongY. CaoX.P. TanL. TanL. Microglial priming in Alzheimer’s disease.Ann. Transl. Med.201861017610.21037/atm.2018.04.2229951498
     [Google Scholar]
  31. HanK. ChapmanS.B. KrawczykD.C. Altered amygdala connectivity in individuals with chronic traumatic brain injury and comorbid depressive symptoms.Front. Neurol.2015623110.3389/fneur.2015.0023126581959
     [Google Scholar]
  32. FannJ.R. HartT. SchomerK.G. Treatment for depression after traumatic brain injury: A systematic review.J. Neurotrauma200926122383240210.1089/neu.2009.109119698070
     [Google Scholar]
  33. McGuireJ.L. NgwenyaL.B. McCullumsmithR.E. Neurotransmitter changes after traumatic brain injury: An update for new treatment strategies.Mol. Psychiatry2019247995101210.1038/s41380‑018‑0239‑630214042
     [Google Scholar]
  34. YueJ. BurkeJ. UpadhyayulaP. WinklerE. DengH. RobinsonC. PirracchioR. SuenC. SharmaS. FergusonA. NgwenyaL. SteinM. ManleyG. TaraporeP. Selective serotonin reuptake inhibitors for treating neurocognitive and neuropsychiatric disorders following traumatic brain injury: An evaluation of current evidence.Brain Sci.2017789310.3390/brainsci708009328757598
     [Google Scholar]
  35. BustoR. DietrichW.D. GlobusM.T. AlonsoO. GinsbergM.D. Extracellular release of serotonin following fluid-percussion brain injury in rats.J. Neurotrauma1997141354210.1089/neu.1997.14.359048309
     [Google Scholar]
  36. ChangC.C. YuS.C. McQuoidD.R. MesserD.F. TaylorW.D. SinghK. BoydB.D. KrishnanK.R.R. MacFallJ.R. SteffensD.C. PayneM.E. Reduction of dorsolateral prefrontal cortex gray matter in late-life depression.Psychiatry Res. Neuroimaging201119311610.1016/j.pscychresns.2011.01.00321596532
     [Google Scholar]
  37. GoyalN. SiddiquiS.V. ChatterjeeU. KumarD. SiddiquiA. Neuropsychology of prefrontal cortex.Indian J. Psychiatry200850320220810.4103/0019‑5545.4363419742233
     [Google Scholar]
  38. JuengstS.B. KumarR.G. WagnerA.K. A narrative literature review of depression following traumatic brain injury: Prevalence, impact, and management challenges.Psychol. Res. Behav. Manag.20171017518610.2147/PRBM.S11326428652833
     [Google Scholar]
  39. BachstetterA.D. BodnarC.N. MorgantiJ.M. Depression following a traumatic brain injury: Uncovering cytokine dysregulation as a pathogenic mechanism.Neural Regen. Res.201813101693170410.4103/1673‑5374.23860430136679
     [Google Scholar]
  40. MooreE.L. Terryberry-SpohrL. HopeD.A. Mild traumatic brain injury and anxiety sequelae: A review of the literature.Brain Inj.200620211713210.1080/0269905050044355816421060
     [Google Scholar]
  41. SooC TateRL Psychological treatment for anxiety in people with traumatic brain injury.Cochrane Database Syst Rev200720073CD00523910.1002/14651858.CD005239.pub2
     [Google Scholar]
  42. MallyaS. SutherlandJ. PongracicS. MainlandB. OrnsteinT.J. The manifestation of anxiety disorders after traumatic brain injury: A review.J. Neurotrauma201532741142110.1089/neu.2014.350425227240
     [Google Scholar]
  43. RodgersK.M. DemingY.K. BercumF.M. ChumachenkoS.Y. WieselerJ.L. JohnsonK.W. WatkinsL.R. BarthD.S. Reversal of established traumatic brain injury-induced, anxiety-like behavior in rats after delayed, post-injury neuroimmune suppression.J. Neurotrauma201431548749710.1089/neu.2013.309024041015
     [Google Scholar]
  44. Van PraagD.L.G. CnossenM.C. PolinderS. WilsonL. MaasA.I.R. Post-traumatic stress disorder after civilian traumatic brain injury: A systematic review and meta-analysis of prevalence rates.J. Neurotrauma201936233220323210.1089/neu.2018.575931238819
     [Google Scholar]
  45. MartindaleS.L. KonstM.J. BatemanJ.R. ArenaA. RowlandJ.A. The role of PTSD and TBI in post-deployment sleep outcomes.Mil. Psychol.202032221222110.1080/08995605.2020.172459538536314
     [Google Scholar]
  46. ChenY. HuangW. Non-impact, blast-induced mild TBI and PTSD: Concepts and caveats.Brain Inj.2011257-864165010.3109/02699052.2011.58031321604927
     [Google Scholar]
  47. BryantR. Post-traumatic stress disorder vs traumatic brain injury.Dialogues Clin. Neurosci.202213325126222034252
     [Google Scholar]
  48. HiottD.W. LabbateL. Anxiety disorders associated with traumatic brain injuries.Neuro Rehabil200217434535510.3233/NRE‑2002‑1740812547982
     [Google Scholar]
  49. MantuaJ HelmsSM WeymannKB Sleep Quality and Emotion Regulation Interact to Predict Anxiety in Veterans with PTSD.Behav Neurol20182018794083210.1155/2018/7940832
     [Google Scholar]
  50. MoreyR.A. GoldA.L. LaBarK.S. BeallS.K. BrownV.M. HaswellC.C. NasserJ.D. WagnerH.R. McCarthyG. Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group.Arch. Gen. Psychiatry201269111169117810.1001/archgenpsychiatry.2012.5023117638
     [Google Scholar]
  51. DavisL.L. SurisA. LambertM.T. HeimbergC. PettyF. Post-traumatic stress disorder and serotonin: New directions for research and treatment.J. Psychiatry Neurosci.19972253183269401312
     [Google Scholar]
  52. BachillerS. Jiménez-FerrerI. PaulusA. YangY. SwanbergM. DeierborgT. Boza-SerranoA. Microglia in neurological diseases: A road map to brain-disease dependent-inflammatory response.Front. Cell. Neurosci.20181248810.3389/fncel.2018.0048830618635
     [Google Scholar]
  53. DonatC.K. ScottG. GentlemanS.M. SastreM. Microglial activation in traumatic brain injury.Front. Aging Neurosci.2017920810.3389/fnagi.2017.0020828701948
     [Google Scholar]
  54. Hernandez-OntiverosD.G. TajiriN. AcostaS. GiuntaB. TanJ. BorlonganC.V. Microglia activation as a biomarker for traumatic brain injury.Front. Neurol.201343010.3389/fneur.2013.0003023531681
     [Google Scholar]
  55. KarveI.P. TaylorJ.M. CrackP.J. The contribution of astrocytes and microglia to traumatic brain injury.Br. J. Pharmacol.2016173469270210.1111/bph.1312525752446
     [Google Scholar]
  56. YoungerD. MuruganM. Rama RaoK.V. WuL.J. ChandraN. Microglia receptors in animal models of traumatic brain injury.Mol. Neurobiol.20195675202522810.1007/s12035‑018‑1428‑730554385
     [Google Scholar]
  57. LoaneD.J. KumarA. Microglia in the TBI brain: The good, the bad, and the dysregulated.Exp. Neurol.20162750 331632710.1016/j.expneurol.2015.08.01826342753
     [Google Scholar]
  58. ChenZ. TrappB.D. Microglia and neuroprotection.J. Neurochem.2016136S1Suppl. 1101710.1111/jnc.1306225693054
     [Google Scholar]
  59. LindholmD. CastrénE. KieferR. ZafraF. ThoenenH. Transforming growth factor-beta 1 in the rat brain: Increase after injury and inhibition of astrocyte proliferation.J. Cell Biol.1992117239540010.1083/jcb.117.2.3951560032
     [Google Scholar]
  60. ZhouZ. PengX. HagshenasJ. InsoleraR. FinkD.J. MataM. A novel cell–cell signaling by microglial transmembrane TNFα with implications for neuropathic pain.Pain2010151229630610.1016/j.pain.2010.06.01720609516
     [Google Scholar]
  61. WoodcockT. Morganti-KossmannM.C. The role of markers of inflammation in traumatic brain injury.Front. Neurol.201341810.3389/fneur.2013.0001823459929
     [Google Scholar]
  62. DinarelloC.A. Proinflammatory Cytokines.Chest2000118250350810.1378/chest.118.2.50310936147
     [Google Scholar]
  63. VaillantA.A. QurieA. Interleukin.Treasure Island, FLStatPearls Publishing2021
     [Google Scholar]
  64. GarlandaC. DinarelloC.A. MantovaniA. The interleukin-1 family: Back to the future.Immunity20133961003101810.1016/j.immuni.2013.11.01024332029
     [Google Scholar]
  65. DinarelloC.A. van der MeerJ.W. Treating inflammation by blocking interleukin-1 in humans.Semin Immunol201325614698410.1016/j.smim.2013.10.008
     [Google Scholar]
  66. ErtaM. QuintanaA. HidalgoJ. Interleukin-6, a major cytokine in the central nervous system.Int. J. Biol. Sci.2012891254126610.7150/ijbs.467923136554
     [Google Scholar]
  67. KumarR.G. DiamondM.L. BolesJ.A. BergerR.P. TishermanS.A. KochanekP.M. WagnerA.K. Acute CSF interleukin-6 trajectories after TBI: Associations with neuroinflammation, polytrauma, and outcome.Brain Behav. Immun.20154525326210.1016/j.bbi.2014.12.02125555531
     [Google Scholar]
  68. ZhouY. FanR. BotchwayB.O.A. ZhangY. LiuX. Infliximab can improve traumatic brain injury by suppressing the tumor necrosis factor alpha pathway.Mol. Neurobiol.20215862803281110.1007/s12035‑021‑02293‑133501626
     [Google Scholar]
  69. RempeR.G. HartzA.M.S. BauerB. Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers.J. Cereb. Blood Flow Metab.20163691481150710.1177/0271678X1665555127323783
     [Google Scholar]
  70. FokinV.F. ShabalinaA.A. PonomarevaN.V. MedvedevR.B. LagodaO.V. TanashyanM.M. Interleukin dynamics during cognitive stress in patients with chronic cerebral ischemia.Bull Russian State Med Univ202020206909610.24075/brsmu.2020.085
     [Google Scholar]
  71. SabatR. GrützG. WarszawskaK. KirschS. WitteE. WolkK. GeginatJ. Biology of interleukin-10.Cytokine Growth Factor Rev.201021533134410.1016/j.cytogfr.2010.09.00221115385
     [Google Scholar]
  72. ThompsonC.D. ZurkoJ.C. HannaB.F. HellenbrandD.J. HannaA. The therapeutic role of interleukin-10 after spinal cord injury.J. Neurotrauma201330151311132410.1089/neu.2012.265123731227
     [Google Scholar]
  73. SongJ. CheonS. JungW. LeeW. LeeJ. Resveratrol induces the expression of interleukin-10 and brain-derived neurotrophic factor in BV2 microglia under hypoxia.Int. J. Mol. Sci.2014159155121552910.3390/ijms15091551225184950
     [Google Scholar]
  74. BurnettA.F. BijuP.G. LuiH. Hauer-JensenM. Oral interleukin 11 as a countermeasure to lethal total-body irradiation in a murine model.Radiat. Res.2013180659560210.1667/RR13330.124219324
     [Google Scholar]
  75. OpalS.M. DePaloV.A. Anti-inflammatory cytokines.Chest200011741162117210.1378/chest.117.4.116210767254
     [Google Scholar]
  76. PuH. ZhengX. JiangX. MuH. XuF. ZhuW. YeQ. JizhangY. HitchensT.K. ShiY. HuX. LeakR.K. DixonC.E. BennettM.V.L. ChenJ. Interleukin-4 improves white matter integrity and functional recovery after murine traumatic brain injury via oligodendroglial PPARγ.J. Cereb. Blood Flow Metab.202141351152910.1177/0271678X2094139332757740
     [Google Scholar]
  77. LiuX. LiuJ. ZhaoS. ZhangH. CaiW. CaiM. JiX. LeakR.K. GaoY. ChenJ. HuX. Interleukin-4 is essential for microglia/macrophage M2 polarization and long-term recovery after cerebral ischemia.Stroke201647249850410.1161/STROKEAHA.115.01207926732561
     [Google Scholar]
  78. XiongX. BarretoG.E. XuL. OuyangY.B. XieX. GiffardR.G. Increased brain injury and worsened neurological outcome in interleukin-4 knockout mice after transient focal cerebral ischemia.Stroke20114272026203210.1161/STROKEAHA.110.59377221597016
     [Google Scholar]
  79. WeberJ.T. Altered calcium signaling following traumatic brain injury.Front. Pharmacol.201236010.3389/fphar.2012.0006022518104
     [Google Scholar]
  80. GurkoffG. ShahlaieK. LyethB. BermanR. Voltage-gated calcium channel antagonists and traumatic brain injury.Pharmaceuticals20136778881210.3390/ph607078824276315
     [Google Scholar]
  81. LiuL. KearnsK.N. EliI. SharifiK.A. SoldozyS. CarlsonE.W. ScottK.W. SluzewskiM.F. ActonS.T. StaudermanK.A. KalaniM.Y.S. ParkM. TvrdikP. Microglial calcium waves during the hyperacute phase of ischemic stroke.Stroke202152127428310.1161/STROKEAHA.120.03276633161850
     [Google Scholar]
  82. NazıroğluM. ŞenolN. GhazizadehV. YürükerV. Neuroprotection induced by N-acetylcysteine and selenium against traumatic brain injury-induced apoptosis and calcium entry in hippocampus of rat.Cell. Mol. Neurobiol.201434689590310.1007/s10571‑014‑0069‑224842665
     [Google Scholar]
  83. ZalewskaT. KanjeM. Edstro¨mA. A calcium-activated neutral protease in the frog nervous system which degrades rapidly transported axonal proteins.Brain Res.19863811586210.1016/0006‑8993(86)90689‑X2428432
     [Google Scholar]
  84. KamakuraK. IshiuraS. ImajohS. NagataN. SugitaH. Distribution of calcium‐activated neutral protease inhibitor in the central nervous system of the rat.J. Neurosci. Res.199231354354810.1002/jnr.4903103181640505
     [Google Scholar]
  85. LeonardS.E. KirbyR. The role of glutamate, calcium and magnesium in secondary brain injury.J. Vet. Emerg. Crit. Care2002121173210.1046/j.1534‑6935.2002.00003.x
     [Google Scholar]
  86. PandyaJ.D. NukalaV.N. SullivanP.G. Concentration dependent effect of calcium on brain mitochondrial bioenergetics and oxidative stress parameters.Front. Neuroenergetics201351010.3389/fnene.2013.0001024385963
     [Google Scholar]
  87. Baracaldo-SantamaríaD. Ariza-SalamancaD.F. Corrales-HernándezM.G. Pachón-LondoñoM.J. Hernandez-DuarteI. Calderon-OspinaC.A. Revisiting excitotoxicity in traumatic brain injury: From bench to bedside.Pharmaceutics202214115210.3390/pharmaceutics1401015235057048
     [Google Scholar]
  88. ChamounR. SukiD. GopinathS.P. GoodmanJ.C. RobertsonC. Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury.J. Neurosurg.2010113356457010.3171/2009.12.JNS0968920113156
     [Google Scholar]
  89. GuerrieroR.M. GizaC.C. RotenbergA. Glutamate and GABA imbalance following traumatic brain injury.Curr. Neurol. Neurosci. Rep.20151552710.1007/s11910‑015‑0545‑125796572
     [Google Scholar]
  90. ZhuangZ. ShenZ. ChenY. DaiZ. ZhangX. MaoY. ZhangB. ZengH. ChenP. WuR. Mapping the changes of glutamate using glutamate chemical exchange saturation transfer (GluCEST) technique in a traumatic brain injury model: A longitudinal pilot study.ACS Chem. Neurosci.201910164965710.1021/acschemneuro.8b0048230346712
     [Google Scholar]
  91. DorsettC.R. McGuireJ.L. NiedzielkoT.L. DePasqualeE.A.K. MellerJ. FloydC.L. McCullumsmithR.E. Traumatic brain injury induces alterations in cortical glutamate uptake without a reduction in glutamate transporter-1 protein expression.J. Neurotrauma201734122023410.1089/neu.2015.437227312729
     [Google Scholar]
  92. Raghavendra RaoV.L. BaşkayaM.K. DoğanA. RothsteinJ.D. DempseyR.J. Traumatic brain injury down-regulates glial glutamate transporter (GLT-1 and GLAST) proteins in rat brain.J. Neurochem.19987052020202710.1046/j.1471‑4159.1998.70052020.x9572288
     [Google Scholar]
  93. JinW. WangH. YanW. ZhuL. HuZ. DingY. TangK. Role of Nrf2 in protection against traumatic brain injury in mice.J. Neurotrauma200926113113910.1089/neu.2008.065519125683
     [Google Scholar]
  94. WangJ. FieldsJ. ZhaoC. LangerJ. ThimmulappaR.K. KenslerT.W. YamamotoM. BiswalS. DoréS. Role of Nrf2 in protection against intracerebral hemorrhage injury in mice.Free Radic. Biol. Med.200743340841410.1016/j.freeradbiomed.2007.04.02017602956
     [Google Scholar]
  95. YanW. WangH.D. HuZ.G. WangQ.F. YinH.X. Activation of Nrf2–ARE pathway in brain after traumatic brain injury.Neurosci. Lett.2008431215015410.1016/j.neulet.2007.11.06018162315
     [Google Scholar]
  96. DongW. YangB. WangL. LiB. GuoX. ZhangM. JiangZ. FuJ. PiJ. GuanD. ZhaoR. Curcumin plays neuroprotective roles against traumatic brain injury partly via Nrf2 signaling.Toxicol. Appl. Pharmacol.2018346283610.1016/j.taap.2018.03.02029571711
     [Google Scholar]
  97. LuX.Y. WangH.D. XuJ.G. DingK. LiT. Deletion of Nrf2 exacerbates oxidative stress after traumatic brain injury in mice.Cell. Mol. Neurobiol.201535571372110.1007/s10571‑015‑0167‑925732597
     [Google Scholar]
  98. ZhangL. WangH. Targeting the NF-E2-related factor 2 pathway: A novel strategy for traumatic brain injury.Mol. Neurobiol.20185521773178510.1007/s12035‑017‑0456‑z28224478
     [Google Scholar]
  99. XuJ. WangH. DingK. ZhangL. WangC. LiT. WeiW. LuX. Luteolin provides neuroprotection in models of traumatic brain injury via the Nrf2–ARE pathway.Free Radic. Biol. Med.20147118619510.1016/j.freeradbiomed.2014.03.00924642087
     [Google Scholar]
  100. DingH. WangH. ZhuL. WeiW. Ursolic acid ameliorates early brain injury after experimental traumatic brain injury in mice by activating the Nrf2 pathway.Neurochem. Res.201742233734610.1007/s11064‑016‑2077‑827734181
     [Google Scholar]
  101. LiuX. LiM. ZhuJ. HuangW. SongJ. Sestrin2 protects against traumatic brain injury by reinforcing the activation of Nrf2 signaling.Hum. Exp. Toxicol.20214071095111110.1177/096032712098422433375867
     [Google Scholar]
  102. ZhangM. AnC. GaoY. LeakR.K. ChenJ. ZhangF. Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection.Prog. Neurobiol.2013100304710.1016/j.pneurobio.2012.09.00323025925
     [Google Scholar]
  103. WadaK. ChatzipanteliK. BustoR. DietrichW.D. Role of nitric oxide in traumatic brain injury in the rat.J. Neurosurg.199889580781810.3171/jns.1998.89.5.08079817419
     [Google Scholar]
  104. HlatkyR. GoodmanJ.C. ValadkaA.B. RobertsonC.S. Role of nitric oxide in cerebral blood flow abnormalities after traumatic brain injury.J. Cereb. Blood Flow Metab.200323558258810.1097/01.WCB.0000059586.71206.F312771573
     [Google Scholar]
  105. OriharaY. IkematsuK. TsudaR. NakasonoI. Induction of nitric oxide synthase by traumatic brain injury.Forensic Sci. Int.20011232-314214910.1016/S0379‑0738(01)00537‑011728740
     [Google Scholar]
  106. SinzE.H. KochanekP.M. DixonC.E. ClarkR.S.B. CarcilloJ.A. SchidingJ.K. ChenM. WisniewskiS.R. CarlosT.M. WilliamsD. DeKoskyS.T. WatkinsS.C. MarionD.W. BilliarT.R. Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice.J. Clin. Invest.1999104564765610.1172/JCI667010487779
     [Google Scholar]
  107. GarryP.S. EzraM. RowlandM.J. WestbrookJ. PattinsonK.T.S. The role of the nitric oxide pathway in brain injury and its treatment — From bench to bedside.Exp. Neurol.201526323524310.1016/j.expneurol.2014.10.01725447937
     [Google Scholar]
  108. VillalbaN. SonkusareS.K. LongdenT.A. TranT.L. SackheimA.M. NelsonM.T. WellmanG.C. FreemanK. Traumatic brain injury disrupts cerebrovascular tone through endothelial inducible nitric oxide synthase expression and nitric oxide gain of function.J. Am. Heart Assoc.201436e00147410.1161/JAHA.114.00147425527626
     [Google Scholar]
  109. MoroM. AlmeidaA. BolañosJ. LizasoainI. Mitochondrial respiratory chain and free radical generation in stroke.Free Radic. Biol. Med.200539101291130410.1016/j.freeradbiomed.2005.07.01016257638
     [Google Scholar]
  110. SchwedhelmE. MaasR. FreeseR. JungD. LukacsZ. JambrecinaA. SpicklerW. SchulzeF. BögerR.H. Pharmacokinetic and pharmacodynamic properties of oral L‐citrulline and L‐arginine: Impact on nitric oxide metabolism.Br. J. Clin. Pharmacol.2008651515910.1111/j.1365‑2125.2007.02990.x17662090
     [Google Scholar]
  111. JeterC.B. HergenroederG.W. WardN.H.III MooreA.N. DashP.K. Human traumatic brain injury alters circulating L-arginine and its metabolite levels: Possible link to cerebral blood flow, extracellular matrix remodeling, and energy status.J. Neurotrauma201229111912710.1089/neu.2011.202921942884
     [Google Scholar]
/content/journals/cnsnddt/10.2174/0118715273318552240708055413
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Neurological Manifestations Following Traumatic Brain Injury: Role of Behavioral, Neuroinflammation, Excitotoxicity, Nrf-2 and Nitric Oxide
CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 24, 47 (2025); https://doi.org/10.2174/0118715273318552240708055413
/content/journals/cnsnddt/10.2174/0118715273318552240708055413
/content/journals/cnsnddt/10.2174/0118715273318552240708055413
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  • Article Type:     Review Article
Keyword(s): and nitric oxide; behavioral changes; excitotoxic changes; neuro-inflammation; Nrf-2; Traumatic brain injury

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