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.)).