Citation

Bolton-Hall AN, Hubbard B, Saatman KE. J. Neurotrauma 2019; 36(8): 1203-1221.

Affiliation

University of Kentucky, SCoBIRC , B367 BBSRB , 741 S. Limestone St. , Lexington, Kentucky, United States , 40536-0509 ; k.saatman@uky.edu.

Copyright

(Copyright © 2019, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2018.6096

PMID

30351225

Abstract

Mild traumatic brain injury (mild TBI) is a growing public concern, as evidence mounts that even head injuries classified as 'mild' can result in persistent neurological dysfunction. Multiple head 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 following 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 the 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 inter-injury 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.

Language: en

Keywords

ANIMAL STUDIES; AXONAL INJURY; Behavior; MODELS OF INJURY; TRAUMATIC BRAIN INJURY