Relationship of mechanical impact magnitude to neurologic dysfunction severity in a rat traumatic brain injury model

PLoS One. 2017 May 26;12(5):e0178186. doi: 10.1371/journal.pone.0178186. eCollection 2017.

Abstract

Objective: Traumatic brain injury (TBI) is a major brain injury type commonly caused by traffic accidents, falls, violence, or sports injuries. To obtain mechanistic insights about TBI, experimental animal models such as weight-drop-induced TBI in rats have been developed to mimic closed-head injury in humans. However, the relationship between the mechanical impact level and neurological severity following weight-drop-induced TBI remains uncertain. In this study, we comprehensively investigated the relationship between physical impact and graded severity at various weight-drop heights.

Approach: The acceleration, impact force, and displacement during the impact were accurately measured using an accelerometer, a pressure sensor, and a high-speed camera, respectively. In addition, the longitudinal changes in neurological deficits and balance function were investigated at 1, 4, and 7 days post TBI lesion. The inflammatory expression markers tested by Western blot analysis, including glial fibrillary acidic protein, beta-amyloid precursor protein, and bone marrow tyrosine kinase gene in chromosome X, in the frontal cortex, hippocampus, and corpus callosum were investigated at 1 and 7 days post-lesion.

Results: Gradations in impact pressure produced progressive degrees of injury severity in the neurological score and balance function. Western blot analysis demonstrated that all inflammatory expression markers were increased at 1 and 7 days post-impact injury when compared to the sham control rats. The severity of neurologic dysfunction and induction in inflammatory markers strongly correlated with the graded mechanical impact levels.

Conclusions: We conclude that the weight-drop-induced TBI model can produce graded brain injury and induction of neurobehavioral deficits and may have translational relevance to developing therapeutic strategies for TBI.

MeSH terms

  • Animals
  • Behavior, Animal
  • Biomechanical Phenomena
  • Brain Injuries, Traumatic / metabolism
  • Brain Injuries, Traumatic / physiopathology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index

Substances

  • Glial Fibrillary Acidic Protein