Relevance of the pre‐clinical models in TBI

Abstract

AbstractIn the absence of any effective translation from preclinical models to clinical application, what has been achieved by laboratory models of TBI? Analysis and assimilation of results from preclinical TBI studies is confounded by the heterogeneity of the models and the TBI paradigms employed. Variance in animal, injury location, severity, number, frequency, age of animal at injury and age of animal at analyses, not to mention the research focus of the investigators themselves, all contribute to the difficulties in data integration and interpretation. Nonetheless, preclinical TBI research has identified areas of focus and enabled creation of timelines of TBI pathobiology. Ultimately, validation of any potential therapeutic targets will require exploitation of the heterogeneity of preclinical models in order to facilitate clinical translation, given the heterogeneity of the patient population.In the course of modeling TBI paradigms in (primarily) mouse models, the failure of recapitulation of TBI‐dependent neurodegenerative pathology representing AD, PD, ALS etc. has prompted the use of mouse models of neurodegenerative disease, expressing genetic risk factors or humanized for proteins implicated in human neurodegenerative diseases, in efforts to understand how TBI can exacerbate or even precipitate the neurodegenerative pathobiology. These investigations have generated many interesting observations, not always easily consolidated into any clear pathogenic mechanism, but some overarching themes have emerged. Some of the published TBI approaches, and findings, will be reviewed, and knowledge gaps and future directions will be discussed.