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Current Neuropharmacology


ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Traumatic Brain Injury Altered Normal Brain Signaling Pathways: Implications for Novel Therapeutics Approaches

Author(s): Arti Rana, Shamsher Singh, Ruchika Sharma and Anoop Kumar*

Volume 17, Issue 7, 2019

Page: [614 - 629] Pages: 16

DOI: 10.2174/1570159X16666180911121847

Price: $65


Traumatic brain injury (TBI) is the main reason of lifelong disability and casualty worldwide. In the United State alone, 1.7 million traumatic events occur yearly, out of which 50,000 results in deaths. Injury to the brain could alter various biological signaling pathways such as excitotoxicity, ionic imbalance, oxidative stress, inflammation, and apoptosis which can result in various neurological disorders such as Psychosis, Depression, Alzheimer disease, Parkinson disease, etc. In literature, various reports have indicated the alteration of these pathways after traumatic brain injury but the exact mechanism is still unclear. Thus, in the first part of this article, we have tried to summarize TBI as a modulator of various neuronal signaling pathways. Currently, very few drugs are available in the market for the treatment of TBI and these drugs only provide the supportive care. Thus, in the second part of the article, based on TBI altered signaling pathways, we have tried to find out potential targets and promising therapeutic approaches in the treatment of TBI.

Keywords: Oxidative stress, excitotoxicity, apoptosis, inflammation, traumatic brain injury, mTOR pathways.

Graphical Abstract
Guerriero, R.M.; Giza, C.C.; Rotenberg, A. Glutamate and GABA imbalance following traumatic brain injury. Curr. Neurol. Neurosci. Rep., 2015, 15(5), 27. []. [PMID: 25796572].
Reis, C.; Gospodarev, V.; Reis, H.; Wilkinson, M.; Gaio, J.; Araujo, C.; Chen, S.; Zhang, J.H. Traumatic brain injury and stem cell: Pathophysiology and update on recent treatment modalities. Stem Cells Int., 2017, 2017, 6392592. [ 2017/6392592]. [PMID: 28852409].
Ahmed, S.; Venigalla, H.; Mekala, H.M.; Dar, S.; Hassan, M.; Ayub, S. Traumatic brain injury and neuropsychiatric complications. Indian J. Psychol. Med., 2017, 39(2), 114-121. [http://dx.]. [PMID: 28515545].
Tanriverdi, F.; Kelestimur, F. Neuroendocrine disturbances after brain damage: an important and often undiagnosed disorder. J. Clin. Med., 2015, 4(5), 847-857. [ jcm4050847]. [PMID: 26239451].
Pearn, M.L.; Niesman, I.R.; Egawa, J.; Sawada, A.; Almenar-Queralt, A.; Shah, S.B.; Duckworth, J.L.; Head, B.P. Pathophysiology associated with traumatic brain injury: current treatments and potential novel therapeutics. Cell. Mol. Neurobiol., 2017, 37(4), 571-585. []. [PMID: 27383839].
Cobb, C.A.; Cole, M.P. Oxidative and nitrative stress in neurodegeneration. Neurobiol. Dis., 2015, 84, 4-21. [ 10.1016/j.nbd.2015.04.020]. [PMID: 26024962].
Pearn, M.L.; Niesman, I.R.; Egawa, J.; Sawada, A.; Almenar-Queralt, A.; Shah, S.B.; Duckworth, J.L.; Head, B.P. Pathophysiology associated with traumatic brain injury: current treatments and potential novel therapeutics. Cell. Mol. Neurobiol., 2017, 37(4), 571-585. []. [PMID: 27383839].
Sinha, V.D.; Chakrabarty, A. Quantitative research on traumatic brain injury in India: The travails and the new optimism. Neurol. India, 2017, 65(2), 261-262. []. [PMID: 28290385].
Marklund, N. Rodent models of traumatic brain injury: methods and challenges Injury Models of the Central Nervous System: Methods and Protocols, 2016. 29-46 [ 978-1-4939-3816-2_3].
Bryan-Hancock, C.; Harrison, J. The global burden of traumatic brain injury: Preliminary results from the global burden of disease project. Inj. Prev., 2010, 16(Suppl. 1), A17-A17. [http://dx.doi. org/10.1136/ip.2010.029215.61].
Lagraoui, M.; Sukumar, G.; Latoche, J.R.; Maynard, S.K.; Dalgard, C.L.; Schaefer, B.C. Salsalate treatment following traumatic brain injury reduces inflammation and promotes a neuroprotective and neurogenic transcriptional response with concomitant functional recovery. Brain Behav. Immun., 2017, 61, 96-109. [http://dx.doi. org/10.1016/j.bbi.2016.12.005]. [PMID: 27939247].
Marklund, N. Rodent models of traumatic brain injury: methods and challenges Injury Models of the Central Nervous System: Methods and Protocols,, 2016. 29-46. [ 978-1-4939-3816-2_3]
Traumatic brain injury-a neurobehavioural sequelae a review Journal of evolution of medical and dental sciences-jemds, 2017, 6 (26), 2192-2207.
Kaur, P.; Sharma, S. Recent advances in pathophysiology of traumatic brain injury. Curr. Neuropharmacol., 2018, 16(8), 1224-1238. [PMID: 28606040].
Lussier, M.P.; Sanz-Clemente, A.; Roche, K.W. Dynamic regulation of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by posttranslational modifications. J. Biol. Chem., 2015, 290(48), 28596-28603. []. [PMID: 26453298].
Schousboe, A.; Scafidi, S.; Bak, L.K.; Waagepetersen, H.S.; McKenna, M.C. Glutamate metabolism in the brain focusing on as trocytes. In: Glutamate and ATP at the Interface of Metabolism and Signaling in the Brain; , 2014. pp. 13-30. [ 1007/978-3-319-08894-5_2]
Herbison, A.E.; Moenter, S.M. Depolarising and hyperpolarising actions of GABA(A) receptor activation on gonadotrophin-releasing hormone neurones: towards an emerging consensus. J. Neuroendocrinol., 2011, 23(7), 557-569. [ 1111/j.1365-2826.2011.02145.x]. [PMID: 21518033].
Shohami, E.; Biegon, A. Novel approach to the role of NMDA receptors in traumatic brain injury CNS & Neurological Disorders- Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders),, 2014, 13 (4), 567-573. [ 18715273113126660196]
Köles, L.; Kató, E.; Hanuska, A.; Zádori, Z.S.; Al-Khrasani, M.; Zelles, T.; Rubini, P.; Illes, P. Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems. Purinergic Signal., 2016, 12(1), 1-24. []. [PMID: 26542977].
Chao, N.; Li, S.T. Synaptic and extrasynaptic glutamate signaling in ischemic stroke. Curr. Med. Chem., 2014, 21(18), 2043-2064. []. [PMID: 24372211].
Katayama, Y.; Becker, D.P.; Tamura, T.; Hovda, D.A. Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J. Neurosurg., 1990, 73(6), 889-900. []. [PMID: 1977896].
Hertz, L. The glutamate–glutamine (GABA) cycle: importance of late postnatal development and potential reciprocal interactions between biosynthesis and degradation. Front. Endocrinol. (Lausanne), 2013, 4, 59. [ 00059]. [PMID: 23750153].
Nani, F.; Bright, D.P.; Revilla-Sanchez, R.; Tretter, V.; Moss, S.J.; Smart, T.G. Tyrosine phosphorylation of GABAA receptor γ2-subunit regulates tonic and phasic inhibition in the thalamus. J. Neurosci., 2013, 33(31), 12718-12727. [ JNEUROSCI.0388-13.2013]. [PMID: 23904608].
Zhang, X.; Chen, Y.; Jenkins, L.W.; Kochanek, P.M.; Clark, R.S. Bench-to-bedside review: Apoptosis/programmed cell death triggered by traumatic brain injury. Crit. Care, 2005, 9(1), 66-75. []. [PMID: 15693986].
Park, Y.H.; Jeong, M.S.; Jang, S.B. Structural insights of homotypic interaction domains in the ligand-receptor signal transduction of tumor necrosis factor (TNF). BMB Rep., 2016, 49(3), 159-166. []. [PMID: 26615973].
Kalimuthu, S.; Se-Kwon, K. Cell survival and apoptosis signaling as therapeutic target for cancer: marine bioactive compounds. Int. J. Mol. Sci., 2013, 14(2), 2334-2354. [ ijms14022334]. [PMID: 23348928].
Belizário, J.; Vieira-Cordeiro, L.; Enns, S. Necroptotic cell death signaling and execution pathway: lessons from knockout mice. Mediators Inflamm., 2015, 2015, 128076. [ 1155/2015/128076]. [PMID: 26491219].
Bhowmick, S.; D’Mello, V.; Ponery, N.; Abdul-Muneer, P.M. Neurodegeneration and sensorimotor deficits in the mouse model of traumatic brain injury. Brain Sci., 2018, 8(1), 1-11. [PMID: 29316623].
Lorente, L. Biomarkers associated with the outcome of traumatic brain injury patients. Brain Sci., 2017, 7(11), 142-153. [http://dx.]. [PMID: 29076989].
Huang, C.Y.; Lee, Y.C.; Li, P.C.; Liliang, P.C.; Lu, K.; Wang, K.W.; Chang, L.C.; Shiu, L.Y.; Chen, M.F.; Sun, Y.T.; Wang, H.K. TDP-43 proteolysis is associated with astrocyte reactivity after traumatic brain injury in rodents. J. Neuroimmunol., 2017, 313, 61-68. []. [PMID: 29153610].
Qiu, J.; Whalen, M.J.; Lowenstein, P.; Fiskum, G.; Fahy, B.; Darwish, R.; Aarabi, B.; Yuan, J.; Moskowitz, M.A. Upregulation of the Fas receptor death-inducing signaling complex after traumatic brain injury in mice and humans. J. Neurosci., 2002, 22(9), 3504-3511. []. [PMID: 11978827].
Weber, J.T. Altered calcium signaling following traumatic brain injury. Front. Pharmacol., 2012, 3, 60. [ fphar.2012.00060]. [PMID: 22518104].
Chehab, T. The role of calcium signalling in autophagy, 2018.
Nazıroğlu, M.; Şenol, N.; Ghazizadeh, V.; Yürüker, V. Neuroprotection induced by N-acetylcysteine and selenium against traumatic brain injury-induced apoptosis and calcium entry in hippocampus of rat. Cell. Mol. Neurobiol., 2014, 34(6), 895-903. [http://dx.]. [PMID: 24842665].
Abdul-Muneer, P.M.; Long, M.; Conte, A.A.; Santhakumar, V.; Pfister, B.J. High Ca2+ influx during traumatic brain injury leads to caspase-1-dependent neuroinflammation and cell death. Mol. Neurobiol., 2017, 54(6), 3964-3975. []. [PMID: 27289225].
Vasco, V.R.L. Role of the phosphoinositide signal transduction pathway in the endometrium. Asian Pac. J. Reprod., 2012, 1(3), 247-252. [].
Ryan, M.J.; Gross, K.W.; Hajduczok, G. Calcium-dependent activation of phospholipase C by mechanical distension in renin-expressing As4. 1 cell. Am. J. Physiol. Endocrinol. Metab., 2000, 279(4), 823-829. [].
Xu, C.; Bailly-Maitre, B.; Reed, J.C. Endoplasmic reticulum stress: cell life and death decisions. J. Clin. Invest., 2005, 115(10), 2656-2664. []. [PMID: 16200199].
Sun, G.Z.; Gao, F.F.; Zhao, Z.M.; Sun, H.; Xu, W.; Wu, L.W.; He, Y.C. Endoplasmic reticulum stress-induced apoptosis in the penumbra aggravates secondary damage in rats with traumatic brain injury. Neural Regen. Res., 2016, 11(8), 1260-1266. [http://dx.doi. org/10.4103/1673-5374.189190]. [PMID: 27651773].
Shi, Z.; Qiu, W.; Xiao, G.; Cheng, J.; Zhang, N. Resveratrol attenuates cognitive deficits of traumatic brain injury by activating p38 signaling in the brain. Med. Sci. Monit., 2018, 24, 1097-1103. []. [PMID: 29467361].
Larner, S.F.; Hayes, R.L.; McKinsey, D.M.; Pike, B.R.; Wang, K.K. Increased expression and processing of caspase-12 after traumatic brain injury in rats. J. Neurochem., 2004, 88(1), 78-90. []. [PMID: 14675152].
Weber, J.T. Altered calcium signaling following traumatic brain injury. Front. Pharmacol., 2012, 3, 60. [ fphar.2012.00060]. [PMID: 22518104].
Zhang, J.; Wang, X.; Vikash, V.; Ye, Q.; Wu, D.; Liu, Y.; Dong, W. ROS and ROS-mediated cellular signaling. Oxid. Med. Cell. Longev., 2016, 2016, 4350965. [ 4350965]. [PMID: 26998193].
Bhattacharyya, A.; Chattopadhyay, R.; Mitra, S.; Crowe, S.E. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol. Rev., 2014, 94(2), 329-354. []. [PMID: 24692350].
Kumar, A.; Sasmal, D.; Sharma, N. An insight into deltamethrin induced apoptotic calcium, p53 and oxidative stress signalling pathways. Toxicol Environ Health Sci, 2015, 7, 25-34. [http://dx.].
Lutton, E.M.; Razmpour, R.; Andrews, A.M.; Cannella, L.A.; Son, Y.J.; Shuvaev, V.V.; Muzykantov, V.R.; Ramirez, S.H. Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury. Sci. Rep., 2017, 7(1), 3846. []. [PMID: 28630485].
Cheng, G.; Kong, R.H.; Zhang, L.M.; Zhang, J.N. Mitochondria in traumatic brain injury and mitochondrial-targeted multipotential therapeutic strategies. Br. J. Pharmacol., 2012, 167(4), 699-719. []. [PMID: 23003569].
Bains, M.; Hall, E.D. Antioxidant therapies in traumatic brain and spinal cord injury. Biochim. Biophys. Acta. Mol. Basis Dis., 2012, 1822(5), 675-684. [].
Clausen, F.; Lundqvist, H.; Ekmark, S.; Lewén, A.; Ebendal, T.; Hillered, L. Oxygen free radical-dependent activation of extracellular signal-regulated kinase mediates apoptosis-like cell death after traumatic brain injury. J. Neurotrauma, 2004, 21(9), 1168-1182. []. [PMID: 15453987].
Huang, Y.N.; Yang, L.Y.; Greig, N.H.; Wang, Y.C.; Lai, C.C.; Wang, J.Y. Neuroprotective effects of pifithrin-α against traumatic brain injury in the striatum through suppression of neuroinflammation, oxidative stress, autophagy, and apoptosis. Sci. Rep., 2018, 8(1), 2368. []. [PMID: 29402897].
Anilkumar, U.; Prehn, J.H. Anti-apoptotic BCL-2 family proteins in acute neural injury. Front. Cell. Neurosci., 2014, 8, 281. []. [PMID: 25324720].
Czabotar, P.E.; Lessene, G.; Strasser, A.; Adams, J.M. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat. Rev. Mol. Cell Biol., 2014, 15(1), 49-63. []. [PMID: 24355989].
Morrison, R.S.; Kinoshita, Y. The role of p53 in neuronal cell death. Cell Death Differ., 2000, 7(10), 868-879. [ 10.1038/sj.cdd.4400741]. [PMID: 11279532].
Sabirzhanov, B.; Zhao, Z.; Stoica, B.A.; Loane, D.J.; Wu, J.; Borroto, C.; Dorsey, S.G.; Faden, A.I. Downregulation of miR-23a and miR-27a following experimental traumatic brain injury induces neuronal cell death through activation of proapoptotic Bcl-2 proteins. J. Neurosci., 2014, 34(30), 10055-10071. [ 10.1523/JNEUROSCI.1260-14.2014]. [PMID: 25057207].
Tehranian, R.; Rose, M.E.; Vagni, V.; Pickrell, A.M.; Griffith, R.P.; Liu, H.; Clark, R.S.; Dixon, C.E.; Kochanek, P.M.; Graham, S.H. Disruption of Bax protein prevents neuronal cell death but produces cognitive impairment in mice following traumatic brain injury. J. Neurotrauma, 2008, 25(7), 755-767. [ 10.1089/neu.2007.0441]. [PMID: 18627254].
Pisetsky, D.S. The translocation of nuclear molecules during inflammation and cell death. Antioxid. Redox Signal., 2014, 20(7), 1117-1125. [].
Karve, I.P.; Taylor, J.M.; Crack, P.J. The contribution of astrocytes and microglia to traumatic brain injury. Br. J. Pharmacol., 2016, 173(4), 692-702. []. [PMID: 25752446].
Corrigan, F.; Mander, K.A.; Leonard, A.V.; Vink, R. Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation. J. Neuroinflammation, 2016, 13(1), 264. []. [PMID: 27724914].
Atkins, C.M.; Oliva, A.A., Jr; Alonso, O.F.; Pearse, D.D.; Bramlett, H.M.; Dietrich, W.D. Modulation of the cAMP signaling pathway after traumatic brain injury. Exp. Neurol., 2007, 208(1), 145-158. []. [PMID: 17916353].
Donat, C.K.; Scott, G.; Gentleman, S.M.; Sastre, M. Microglial activation in traumatic brain injury. Front. Aging Neurosci., 2017, 9, 208. []. [PMID: 28701948].
Don, A.S.A.; Tsang, C.K.; Kazdoba, T.M.; D’Arcangelo, G.; Young, W.; Zheng, X.F. Targeting mTOR as a novel therapeutic strategy for traumatic CNS injuries. Drug Discov. Today, 2012, 17(15-16), 861-868. [ 010]. [PMID: 22569182].
Garza-Lombó, C.; Gonsebatt, M.E. Mammalian target of rapamycin: its role in early neural development and in adult and aged brain function. Front. Cell. Neurosci., 2016, 10, 157. [ 10.3389/fncel.2016.00157]. [PMID: 27378854].
Lake, D.; Corrêa, S.A.; Müller, J. Negative feedback regulation of the ERK1/2 MAPK pathway. Cell. Mol. Life Sci., 2016, 73(23), 4397-4413. []. [PMID: 27342992].
Don, A.S.A.; Tsang, C.K.; Kazdoba, T.M.; D’Arcangelo, G.; Young, W.; Zheng, X.F. Targeting mTOR as a novel therapeutic strategy for traumatic CNS injuries. Drug Discov. Today, 2012, 17(15-16), 861-868. [ 010]. [PMID: 22569182].
Wang, X.; Seekaew, P.; Gao, X.; Chen, J. Traumatic brain injury stimulates neural stem cell proliferation via mammalian target of rapamycin signaling pathway activation. eNeuro, 2016, 3(5), 1-14. []. [PMID: 27822507].
Sun, J.; Nan, G. The extracellular signal-regulated kinase 1/2 pathway in neurological diseases: A potential therapeutic target.(Review). Int. J. Mol. Med., 2017, 39(6), 1338-1346. [ 10.3892/ijmm.2017.2962]. [PMID: 28440493].
Leisman, G.; Moustafa, A.A.; Shafir, T. Thinking, walking, talking: integratory motor and cognitive brain function. Front. Public Health, 2016, 4, 94. []. [PMID: 27252937].
Ahmed, S.; Venigalla, H.; Mekala, H.M.; Dar, S.; Hassan, M.; Ayub, S. Traumatic brain injury and neuropsychiatric complications. Indian J. Psychol. Med., 2017, 39(2), 114-121. [http://dx.]. [PMID: 28515545].
Onwuchekwa, C.R.; Alazigha, N.S. Computed tomography pattern of traumatic head injury in Niger Delta, Nigeria: A multicenter evaluation. Int. J. Crit. Illn. Inj. Sci., 2017, 7(3), 150-155. []. [PMID: 28971028].
Nayebaghayee, H.; Afsharian, T. Correlation between Glasgow Coma Scale and brain computed tomography-scan findings in head trauma patients. Asian J. Neurosurg., 2016, 11(1), 46-49. []. [PMID: 26889279].
Agoston, D.V.; Shutes-David, A.; Peskind, E.R. Biofluid biomarkers of traumatic brain injury. Brain Inj., 2017, 31(9), 1195-1203. []. [PMID: 28981341].
Carney, N.; Totten, A.M.; O’Reilly, C.; Ullman, J.S.; Hawryluk, G.W.; Bell, M.J.; Bratton, S.L.; Chesnut, R.; Harris, O.A.; Kissoon, N.; Rubiano, A.M.; Shutter, L.; Tasker, R.C.; Vavilala, M.S.; Wilberger, J.; Wright, D.W.; Ghajar, J. Guidelines for the management of severe traumatic brain injury. Neurosurgery, 2017, 80(1), 6-15. [PMID: 27654000].
Shirley, R.; Ord, E.N.; Work, L.M. Oxidative stress and the use of antioxidants in stroke. Antioxidants, 2014, 3(3), 472-501. []. [PMID: 26785066].
Lin, C.J.; Chen, T.H.; Yang, L.Y.; Shih, C.M. Resveratrol protects astrocytes against traumatic brain injury through inhibiting apoptotic and autophagic cell death. Cell Death Dis., 2014, 5(3), e1147. []. [PMID: 24675465].
Venegoni, W.; Shen, Q.; Thimmesch, A.R.; Bell, M.; Hiebert, J.B.; Pierce, J.D. The use of antioxidants in the treatment of traumatic brain injury. J. Adv. Nurs., 2017, 73(6), 1331-1338. [http://dx.doi. org/10.1111/jan.13259]. [PMID: 28103389].
Arifin, M.Z.; Faried, A.; Shahib, M.N.; Wiriadisastra, K.; Bisri, T. Inhibition of activated NR2B gene- and caspase-3 protein-expression by glutathione following traumatic brain injury in a rat model. Asian J. Neurosurg., 2011, 6(2), 72-77. [ 10.4103/1793-5482.92160]. [PMID: 22347327].
Pereira-Leite, C.; Nunes, C.; Jamal, S.K.; Cuccovia, I.M.; Reis, S. Nonsteroidal anti‐inflammatory therapy: a journey toward safety. Med. Res. Rev., 2017, 37(4), 802-859. [ med.21424]. [PMID: 28005273].
Thelin, E.P.; Hall, C.E.; Gupta, K.; Carpenter, K.L.H.; Chandran, S.; Hutchinson, P.J.; Patani, R.; Helmy, A. Elucidating pro-inflammatory cytokine responses after traumatic brain injury in a human stem cell model. J. Neurotrauma, 2018, 35(2), 341-352. []. [PMID: 28978285].
Wilson, N.M.; Gurney, M.E.; Dietrich, W.D.; Atkins, C.M. Therapeutic benefits of phosphodiesterase 4B inhibition after traumatic brain injury. PLoS One, 2017, 12(5), e0178013. [ 10.1371/journal.pone.0178013]. [PMID: 28542295].
Garrido-Mesa, N.; Zarzuelo, A.; Gálvez, J. Minocycline: far beyond an antibiotic. Br. J. Pharmacol., 2013, 169(2), 337-352. []. [PMID: 23441623].
Lei, B.; Mace, B.; Dawson, H.N.; Warner, D.S.; Laskowitz, D.T.; James, M.L. Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia. PLoS One, 2014, 9(7), e103969. []. [PMID: 25080336].
Trippier, P.C.; Jansen Labby, K.; Hawker, D.D.; Mataka, J.J.; Silverman, R.B. Target- and mechanism-based therapeutics for neurodegenerative diseases: strength in numbers. J. Med. Chem., 2013, 56(8), 3121-3147. []. [PMID: 23458846].
Haar, C.V.; Peterson, T.C.; Martens, K.M.; Hoane, M.R. The use of nicotinamide as a treatment for experimental traumatic brain injury and stroke: A review and evaluation. Clin. Pharmacol. Biopharmaceut. S, 2013, 1(2), 1-8.
Xu, X.; Gao, W.; Cheng, S.; Yin, D.; Li, F.; Wu, Y.; Sun, D.; Zhou, S.; Wang, D.; Zhang, Y.; Jiang, R.; Zhang, J. Anti-inflammatory and immunomodulatory mechanisms of atorvastatin in a murine model of traumatic brain injury. J. Neuroinflammation, 2017, 14(1), 167-182. []. [PMID: 28835272].
Siopi, E.; Cho, A.H.; Homsi, S.; Croci, N.; Plotkine, M.; Marchand-Leroux, C.; Jafarian-Tehrani, M. Minocycline restores sAPPα levels and reduces the late histopathological consequences of traumatic brain injury in mice. J. Neurotrauma, 2011, 28(10), 2135-2143. []. [PMID: 21770756].
Wang, C.; Hu, Z.; Zou, Y.; Xiang, M.; Jiang, Y.; Botchway, B.O.A.; Huo, X.; Du, X.; Fang, M. The post-therapeutic effect of rapamycin in mild traumatic brain-injured rats ensuing in the upregulation of autophagy and mitophagy. Cell Biol. Int., 2017, 41(9), 1039-1047. []. [PMID: 28685977].
Erlich, S.; Alexandrovich, A.; Shohami, E.; Pinkas-Kramarski, R. Rapamycin is a neuroprotective treatment for traumatic brain injury. Neurobiol. Dis., 2007, 26(1), 86-93. [ 1016/j.nbd.2006.12.003]. [PMID: 17270455].
Zhu, X.; Park, J.; Golinski, J.; Qiu, J.; Khuman, J.; Lee, C.C.; Lo, E.H.; Degterev, A.; Whalen, M.J. Role of Akt and mammalian target of rapamycin in functional outcome after concussive brain injury in mice. J. Cereb. Blood Flow Metab., 2014, 34(9), 1531-1539. []. [PMID: 24938400].
Shi, G.D. OuYang, Y.P.; Shi, J.G.; Liu, Y.; Yuan, W.; Jia, L.S. PTEN deletion prevents ischemic brain injury by activating the mTOR signaling pathway. Biochem. Biophys. Res. Commun., 2011, 404(4), 941-945. []. [PMID: 21185267].
You, W.; Wang, Z.; Li, H.; Shen, H.; Xu, X.; Jia, G.; Chen, G. Inhibition of mammalian target of rapamycin attenuates early brain injury through modulating microglial polarization after experimental subarachnoid hemorrhage in rats. J. Neurol. Sci., 2016, 367, 224-231. []. [PMID: 27423593].
Gurkoff, G.; Shahlaie, K.; Lyeth, B.; Berman, R. Voltage-gated calcium channel antagonists and traumatic brain injury. Pharmaceuticals (Basel), 2013, 6(7), 788-812. [ ph6070788]. [PMID: 24276315].
Hoshide, R.; Cheung, V.; Marshall, L.; Kasper, E.; Chen, C.C. Do corticosteroids play a role in the management of traumatic brain injury? Surg. Neurol. Int., 2016, 7, 84. []. [PMID: 27656315].
Wu, C.; Sun, D. GABA receptors in brain development, function, and injury. Metab. Brain Dis., 2015, 30(2), 367-379. [http://dx.doi. org/10.1007/s11011-014-9560-1]. [PMID: 24820774].
Dutertre, S.; Becker, C.M.; Betz, H. Inhibitory glycine receptors: an update. J. Biol. Chem., 2012, 287(48), 40216-40223. [http://dx.]. [PMID: 23038260].
Dorsett, C.R.; McGuire, J.L.; DePasquale, E.A.; Gardner, A.E.; Floyd, C.L.; McCullumsmith, R.E. Glutamate neurotransmission in rodent models of traumatic brain injury. J. Neurotrauma, 2017, 34(2), 263-272. []. [PMID: 27256113].
Chunhua, C.; Chunhua, X.; Megumi, S.; Renyu, L. Kappa opioid receptor agonist and brain ischemia. Transl. Perioper. Pain Med., 2014, 1(2), 27-34. [PMID: 25574482].
Plesnila, N.; von Baumgarten, L.; Retiounskaia, M.; Engel, D.; Ardeshiri, A.; Zimmermann, R.; Hoffmann, F.; Landshamer, S.; Wagner, E.; Culmsee, C. Delayed neuronal death after brain trauma involves p53-dependent inhibition of NF-kappaB transcriptional activity. Cell Death Differ., 2007, 14(8), 1529-1541. [http://dx.doi. org/10.1038/sj.cdd.4402159]. [PMID: 17464322].
Yang, L.Y.; Greig, N.H.; Huang, Y.N.; Hsieh, T.H.; Tweedie, D.; Yu, Q.S.; Hoffer, B.J.; Luo, Y.; Kao, Y.C.; Wang, J.Y. Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury. Neurobiol. Dis., 2016, 96, 216-226. [ 012]. [PMID: 27553877].
Huang, X.J.; Li, W.P.; Lin, Y.; Feng, J.F.; Jia, F.; Mao, Q.; Jiang, J.Y. Blockage of the upregulation of voltage-gated sodium channel nav1. 3 improve outcomes after experimental traumatic brain injury. J. Neurotrauma, 2014, 31(4), 346-357.
Wahl, F.; Renou, E.; Mary, V.; Stutzmann, J.M. Riluzole reduces brain lesions and improves neurological function in rats after a traumatic brain injury. Brain Res., 1997, 756(1-2), 247-255. [http://]. [PMID: 9187339].
Stocchetti, N.; Carbonara, M.; Citerio, G.; Ercole, A.; Skrifvars, M.B.; Smielewski, P.; Zoerle, T.; Menon, D.K. Severe traumatic brain injury: targeted management in the intensive care unit. Lancet Neurol., 2017, 16(6), 452-464. []. [PMID: 28504109].
Xiong, Y.; Zhang, Y.; Mahmood, A.; Chopp, M. Investigational agents for treatment of traumatic brain injury. Expert Opin. Investig. Drugs, 2015, 24(6), 743-760. [ 13543784.2015.1021919]. [PMID: 25727893].
Zhu, H.T.; Bian, C.; Yuan, J.C.; Chu, W.H.; Xiang, X.; Chen, F.; Wang, C.S.; Feng, H.; Lin, J.K. Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury. J. Neuroinflammation, 2014, 11(1), 59. []. [PMID: 24669820].

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