The Effects of Early Post-Traumatic Hyperthermia in Female and Ovariectomized Rats

Episodes of post-traumatic hyperthermia commonly occur in the head-injured patient population. Although post-traumatic hyperthermia has been shown to worsen outcome in experimental studies using male rats, the consequences of secondary hyperthermia following traumatic brain injury (TBI) have not been investigated in female animals. Thus, the purpose of this study was to examine the effects of post-traumatic hyperthermia after fluid-percussion (F-P) brain injury in intact and ovariectomized female rats. Thirty-eight female Sprague-Dawley rats were used in these experiments. Intact female rats underwent TBI followed 30 min later by a 4-h period of normothermia (37°C) or brain hyperthermia (40°C). Female rats that had been ovariectomized 10 days prior to TBI were also traumatized and followed by a period of normothermia or hyperthermia. At 72 h after TBI, rats were perfusion-fixed for quantitative histopathological and immunocytochemical evaluation. Following normothermic TBI, intact female rats demonstrated significantly smaller contusion volumes, decreased frequency of axonal beta-amyloid precursor protein (β-APP) profiles, and greater numbers of NeuN-positive cortical neurons compared to traumatized ovariectomized females. Although post-traumatic hyperthermia increased contusion volume, cortical neuronal cell death and axonal damage in both intact and ovariectomized female groups, the effects of the induced hyperthermic period were more pronounced in ovariectomized animals. These findings demonstrate for the first time that post-traumatic hyperthermia worsens histopathological outcome in female rats, and that neural hormones, including estrogen and progesterone, may protect against secondary hyperthermic insults.