The importance of gender on the beneficial effects of posttraumatic hypothermia

The authors studied the importance of gender on the consequences of mild posttraumatic hypothermia following parasagittal fluid-percussion (F-P) brain injury in rats. After traumatic brain injury (TBI), brain temperature was maintained at normothermia (37 degrees C) or reduced to 33 degrees C for 4 h starting 30 min after the insult followed by a 1.5-h slow rewarming period. Animals (n = 48) were allowed to survive for 3 days before quantitative histopathological and immunocytochemical examination. As previously reported, contusion volume in normothermic animals (37 degrees C) was smaller (P < 0.05) in intact females compared to males. In addition, numbers of NeuN-positive cortical neurons were greater in females versus males after TBI. Posttraumatic hypothermia significantly reduced overall contusion volume in males (P < 0.05), while not significantly reducing contusion volume in females. Likewise, hypothermia protected against the loss of cortical neurons in males but had no effect in females. Ovariectomized females showed contusion volumes and neuronal cell counts comparable to those seen in males as well as a significant reduction in contusion volumes and greater neuronal counts following posttraumatic hypothermia. These data are the first to demonstrate that posttraumatic hypothermia (4 h) does not affect short-term histopathological outcomes in female rats. Potential mechanisms underlying this gender difference are discussed. Finally, these experimental findings may have important implications in terms of clinical trials using therapeutic hypothermia targeting patients with central nervous system (CNS) injury.