Experimental Designs for Repeated Mild Traumatic Brain Injury: Challenges and Considerations

Amanda N. Bolton-Hall, W. Brad Hubbard, Kathryn E. Saatman

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


Mild traumatic brain injury (mild TBI) is a growing public concern, as evidence mounts that even brain injuries classified as "mild" can result in persistent neurological dysfunction. Multiple brain injuries heighten the likelihood of worsened or more prolonged symptomatology and may trigger long-term neurodegeneration. Animal models provide a logical platform to identify key parameters, such as loading forces, duration between injuries, and number of injuries, which contribute to additive or synergistic damage after repeated mild TBI. Despite the tremendous increase in research productivity in the field of repeated mild TBI, relatively few studies have been designed in such a way as to provide experimental-based insights into the dependence of cellular and functional outcomes on the prescribed parameters of mild TBI. In this review, we summarize how standard models of TBI have been adapted to produce mild TBI and highlight commonly observed aspects of neuropathology replicated in rodent models of mild TBI. The complexity of designing studies of repeated TBI is discussed, including challenges of incorporating appropriate control groups, informative experimental design, and relevant outcome measures. We then feature studies that provide a well-controlled, within-study design varying either the number of injuries or the interinjury interval. Harnessing the power of experimental models of TBI to elucidate which injury parameters are critical contributors to acute and chronic damage after repeated injury can further efforts at prevention and provide improved models for testing mechanisms and therapeutic interventions.

Original languageEnglish
Pages (from-to)1203-1221
Number of pages19
JournalJournal of Neurotrauma
Issue number8
StatePublished - Apr 15 2019

Bibliographical note

Publisher Copyright:
© Copyright 2019, Mary Ann Liebert, Inc.


  • axonal injury
  • cortex
  • hippocampus
  • memory loss
  • neuroinflammation
  • rodent behavior

ASJC Scopus subject areas

  • Clinical Neurology


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