Evidence for the therapeutic efficacy of either mild hypothermia or oxygen radical scavengers after repetitive mild traumatic brain injury

J Neurotrauma. 2014 Apr 15;31(8):773-81. doi: 10.1089/neu.2013.3181. Epub 2014 Feb 7.


Repetitive brain injury, particularly that occurring with sporting-related injuries, has recently garnered increased attention in both the clinical and public settings. In the laboratory, we have demonstrated the adverse axonal and vascular consequences of repetitive brain injury and have demonstrated that moderate hypothermia and/or FK506 exerted protective effects after repetitive mild traumatic brain injury (mTBI) when administered within a specific time frame, suggesting a range of therapeutic modalities to prevent a dramatic exacerbation. In this communication, we revisit the utility of targeted therapeutic intervention to seek the minimal level of hypothermia needed to achieve protection while probing the role of oxygen radicals and their therapeutic targeting. Male Sprague-Dawley rats were subjected to repetitive mTBI by impact acceleration injury. Mild hypothermia (35 °C, group 2), superoxide dismutase (group 3), and Tempol (group 4) were employed as therapeutic interventions administered 1 h after the repetitive mTBI. To assess vascular function, cerebral vascular reactivity to acetylcholine was evaluated 3 and 4 h after the repetitive mTBI, whereas to detect the burden of axonal damage, amyloid precursor protein (APP) density in the medullospinal junction was measured. Whereas complete impairment of vascular reactivity was observed in group 1 (without intervention), significant preservation of vascular reactivity was found in the other groups. Similarly, whereas remarkable increase in the APP-positive axon was observed in group 1, there were no significant increases in the other groups. Collectively, these findings indicate that even mild hypothermia or the blunting free radical damage, even when performed in a delayed period, is protective in repetitive mTBI.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / pathology
  • Brain / physiopathology
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology*
  • Disease Models, Animal
  • Free Radical Scavengers / pharmacology*
  • Hypothermia, Induced*
  • Immunohistochemistry
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tacrolimus / pharmacology*


  • Free Radical Scavengers
  • Tacrolimus