Mild hyperthermia worsens the neuropathological damage associated with mild traumatic brain injury in rats

Atsushi Sakurai, Coleen M. Atkins, Ofelia F. Alonso, Helen M. Bramlett, W. Dalton Dietrich

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


The effects of slight variations in brain temperature on the pathophysiological consequences of acute brain injury have been extensively described in models of moderate and severe traumatic brain injury (TBI). In contrast, limited information is available regarding the potential consequences of temperature elevations on outcome following mild TBI (mTBI) or concussions. One potential confounding variable with mTBI is the presence of elevated body temperature that occurs in the civilian or military populations due to hot environments combined with exercise or other forms of physical exertion. We therefore determined the histopathological effects of pre- and post-traumatic hyperthermia (39°C) on mTBI. Adult male Sprague-Dawley rats were divided into 3 groups: pre/post-traumatic hyperthermia, post-traumatic hyperthermia alone for 2h, and normothermia (37°C). The pre/post-hyperthermia group was treated with hyperthermia starting 15min before mild parasagittal fluid-percussion brain injury (1.4-1.6 atm), with the temperature elevation extending for 2h after trauma. At 72h after mTBI, the rats were perfusion-fixed for quantitative histopathological evaluation. Contusion areas and volumes were significantly larger in the pre/post-hyperthermia treatment group compared to the post-hyperthermia and normothermic groups. In addition, pre/post-traumatic hyperthermia caused the most severe loss of NeuN-positive cells in the dentate hilus compared to normothermia. These neuropathological results demonstrate that relatively mild elevations in temperature associated with peri-traumatic events may affect the long-term functional consequences of mTBI. Because individuals exhibiting mildly elevated core temperatures may be predisposed to aggravated brain damage after mTBI or concussion, precautions should be introduced to target this important physiological variable.

Original languageEnglish (US)
Pages (from-to)313-321
Number of pages9
JournalJournal of neurotrauma
Issue number2
StatePublished - Jan 20 2012


  • concussion
  • dentate hilus
  • fluid-percussion brain injury
  • hyperthermia
  • temperature
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology


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