Posttraumatic hypothermia is neuroprotective in a model of traumatic brain injury complicated by a secondary hypoxic insult

Objective: Human traumatic brain injury frequently results in secondary complications, including hypoxia. In previous studies, we have reported that posttraumatic hypothermia is neuroprotective and that secondary hypoxia exacerbates histopathologic outcome after fluid-percussion brain injury. The purpose of this study was to assess the therapeutic effects of mild (33°C) hypothermia after fluid-percussion injury combined with secondary hypoxia. In addition, the importance of the rewarming period on histopathologic outcome was investigated. Design: Prospective experimental study in rats. Setting: Experimental laboratory in a university teaching hospital. Intervention: Intubated, anesthetized rats underwent normothermic parasagittal fluid-percussion brain injury (1.8-2.1 atmospheres) followed by either 30 mins of normoxia (n = 6) or hypoxic (n = 6) gas levels and by 4 hrs of normothermia (37°C). In hypothermic rats, brain temperature was reduced immediately after the 30-min hypoxic insult and maintained for 4 hrs. After hypothermia, brain temperature was either rapidly (n = 6) or slowly (n = 5) increased to normothermic levels. Rats were killed 3 days after traumatic brain injury, and contusion volumes were quantitatively assessed. Measurements and Main Results: As previously shown, posttraumatic hypoxia significantly increased contusion volume compared with traumatic brain injury-normoxic animals (p < .02). Importantly, although posttraumatic hypothermia followed by rapid rewarming (15 mins) failed to decrease contusion volume, those animals undergoing a slow rewarming period (120 mins) demonstrated significantly (p < .03) reduced contusion volumes, compared with hypoxic normothermic rats. Conclusions: These data emphasize the beneficial effects of posttraumatic hypothermia in a traumatic brain injury model complicated by secondary hypoxia and stress the importance of the rewarming period in this therapeutic intervention.