Roadmap for Advancing Pre-Clinical Science in Traumatic Brain Injury

Douglas H. Smith*, Patrick M. Kochanek, Susanna Rosi, Retsina Meyer, Chantelle Ferland-Beckham, Eric M. Prager, Stephen T. Ahlers, Fiona Crawford*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Pre-clinical models of disease have long played important roles in the advancement of new treatments. However, in traumatic brain injury (TBI), despite the availability of numerous model systems, translation from bench to bedside remains elusive. Integrating clinical relevance into pre-clinical model development is a critical step toward advancing therapies for TBI patients across the spectrum of injury severity. Pre-clinical models include in vivo and ex vivo animal work-both small and large- A nd in vitro modeling. The wide range of pre-clinical models reflect substantial attempts to replicate multiple aspects of TBI sequelae in humans. Although these models reveal multiple putative mechanisms underlying TBI pathophysiology, failures to translate these findings into successful clinical trials call into question the clinical relevance and applicability of the models. Here, we address the promises and pitfalls of pre-clinical models with the goal of evolving frameworks that will advance translational TBI research across models, injury types, and the heterogenous etiology of pathology.

Original languageEnglish
Pages (from-to)3204-3221
Number of pages18
JournalJournal of Neurotrauma
Issue number23
StatePublished - Dec 2021
Externally publishedYes


  • diffuse axonal injury
  • neurodegeneration, neuroinflammation
  • neurological dysfunction
  • pre-clinical animal models
  • traumatic brain injury


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