Cerebral vascular responsiveness after experimental traumatic brain injury: the beneficial effects of delayed hypothermia combined with superoxide dismutase administration.

OBJECT: Traumatic brain injury (TBI) induces cerebral vascular dysfunction reflected in altered responses to vasodilators such as acetylcholine and hypercapnia. It has been demonstrated that the use of either posttraumatic hypothermia or free radical scavengers offered vascular protection when those treatments were delivered early after the injury, losing efficacy when the initiation of either treatment was delayed. Because immediate posttraumatic treatment is not realistic in the clinical setting, the authors undertook this study to investigate whether the combination of delayed hypothermia and the delayed administration of the free radical scavenger superoxide dismutase (SOD) could result in improved vascular protection. METHODS: Male Sprague-Dawley rats were anesthetized and subjected to either an impact-acceleration or sham injury. Animals were treated either with hypothermia (32 degrees C) initiated 60 minutes after TBI, delayed SOD (60 U/ml) applied 90 minutes after TBI, or a combination of delayed hypothermia (32 degrees C) and delayed SOD (60 U/ml) applied 15 minutes prior to the cessation of hypothermia. In this investigation, the diameter of cerebral pial arterioles was measured at rest and then challenged with vasodilator acetylcholine and hypercapnia. Four vessels were assessed per animal prior to injury and then again up to 6 hours after injury. RESULTS: Delayed SOD treatment did not enhance vascular function, while delayed hypothermia treatment only partially preserved pial vascular function. However, the combination of delayed hypothermia and delayed SOD significantly preserved vascular function after the injury. CONCLUSIONS: The results of these studies demonstrate that delayed hypothermia partially preserves vascular function after TBI, while expanding the therapeutic window over which agents such as SOD can now provide enhanced protection.