====== Neuroprotection for Traumatic Brain Injury ======
Treatments and [[neuroprotection]] following [[Traumatic brain injury]] (TBI) are limited because [[secondary injury]] cascades are poorly understood. 

Neuroprotective treatments that limit secondary tissue loss and/or improve behavioral outcomes have been well established in multiple animal models of TBI. However, the translation of such neuroprotective strategies to human injury has been disappointing, with the failure of more than thirty controlled clinical trials. Both conceptual issues and methodological differences between preclinical and clinical injury have undoubtedly contributed to these translational difficulties
((Loane DJ, Faden AI. Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends Pharmacol Sci. 2010 Dec;31(12):596-604. doi: 10.1016/j.tips.2010.09.005. Epub 2010 Oct 29. PMID: 21035878; PMCID: PMC2999630.)).
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Evaluating novel compounds for [[neuroprotective]] effects in [[animal model]]s of [[traumatic brain injury]] (TBI) is a protracted, labor-intensive, and costly effort. However, the present lack of effective options for [[traumatic brain injury treatment]], despite decades of  [[traumatic brain injury research]], shows the critical need for alternative methods for [[screening]] new [[drug]] candidates with neuroprotective properties. Because natural products have been a leading source of new therapeutic agents for human diseases, Weisz et al. used an [[in vitro]] model of stretch injury to rapidly assess the pro-survival effects of three [[bioactive]] compounds, two isolated from natural products ([[clovanemagnolol]] [CM], [[vinaxanthone]] [VX]) and the third, a dietary compound ([[pterostilbene]] [PT]) found in [[blueberry]]. The [[stretch injury]] experiments were not used to validate drug efficacy in a comprehensive manner but used primarily, as proof-of-principle, to demonstrate that the neuroprotective potential of each bioactive agent can be quickly assessed in an immortalized hippocampal cell line in lieu of comprehensive testing in animal models of TBI. To gain mechanistic insights into potential molecular mechanisms of neuroprotective effects, they performed a pathway-specific [[PCR]] [[array]] analysis of the effects of CM on the rat [[hippocampus]] and [[microRNA]] [[sequencing]] analysis of the effects of VX and PT on cultured hippocampal [[neural progenitor cells]]. They showed that the neuroprotective properties of these natural compounds are associated with the altered expression of several genes or microRNAs that have functional roles in [[neurodegeneration]] or [[cell]] [[survival]]. The approach could help in quickly assessing multiple natural products for neuroprotective properties and expedite the process of new [[drug]] discovery for [[traumatic brain injury treatment]]
((Weisz HA, Boone DR, Coggins WS, Edwards GA, Willey HE, Widen SG, Siegel D, Nelson AT, Prough DS, Hellmich HL. Mechanistic insights gained from [[cell]] and molecular analysis of the [[neuroprotective]] potential of bioactive natural compounds in an immortalized hippocampal [[cell line]]. PLoS One. 2022 Jun 3;17(6):e0267682. doi: 10.1371/journal.pone.0267682. PMID: 35657963.)).
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Management is based on weak evidence, with little attempt to personalize treatment. A need exists for new [[precision medicine]] and stratified management approaches that incorporate emerging technologies.


Some drugs such as [[corticosteroid]]s and [[progesterone]] have already been investigated in TBI [[neuroprotection]] but failed to demonstrate clinical applicability in advanced phases of the studies. Dietary antioxidants, such as curcumin, [[resveratrol]], and sulforaphane, have been shown to attenuate [[traumatic brain injury]]-induced damage in preclinical studies. These dietary antioxidants can increase antioxidant defenses via transcriptional activation of NRF2 and are also known as carbonyl scavengers, two potential mechanisms for neuroprotection
((Mendes Arent A, de Souza LF, Walz R, Dafre AL. Perspectives on Molecular
Biomarkers of Oxidative Stress and Antioxidant Strategies in Traumatic Brain
Injury. Biomed Res Int. 2014;2014:723060. Epub 2014 Feb 13. Review. PubMed PMID: 
24689052.
)).

===Hypothermia===
see [[Hypothermia]].

==Valproate==

Several studies have indicated that 300 mg/kg or 400 mg/kg of valproate (VPA) exhibits neuroprotective effects in animal models. However, humans cannot tolerate high doses of VPA. 

A study found that 30 mg/kg of VPA assists in treating TBIs in rat models
((Tai YT, Lee WY, Lee FP, Lin TJ, Shih CL, Wang JY, Chiu WT, Hung KS. Low dose
of valproate improves motor function after traumatic brain injury. Biomed Res
Int. 2014;2014:980657. doi: 10.1155/2014/980657. Epub 2014 Feb 6. PubMed PMID:
24689067.)).