The purpose of this proposal is to evaluate the effect of a secondary ischemic insult on the previously traumatized brain in order to determine if head trauma renders the central nervous system more vulnerable to ischemic brain damage. Secondly, we will determine if post-traumatic serum hyperglycemia plays a major role in the vulnerability of the traumatized brain to ischemia. Lastly, we will determine if the manipulation of serum glucose levels following head injury employing insulin administration decreases the risk of the traumatized brain to secondary ischemic insults. Through such studies we will test our hypotheses: 1) that the traumatized brain is more vulnerable to ischemic injury than the normal brain; 2) that the increased vulnerability of the brain to ischemia following head injury is primarily the result of serum hyperglycemia; 3) that by decreasing serum glucose levels with insulin administration following head trauma, the vulnerability of the brain to secondary ischemia will be significantly reduced. By combining a model of fluid percussion head injury and a model of global incomplete cerebral ischemia induced by hemorrhagic hypotension, we propose to produce a consistent and mild to moderate level of head trauma followed by a consistent level of incomplete ischemia for a 7-minute period. Traumatic and ischemic brain injury will be assessed both separately and in combination by employing measurements of total and regional CBF with 15 Mum microspheres, multimodality evoked potentials, regional quantitative morphometric neuropathology, and regional assessments of brain energy metabolites. CBF and evoked potentials will be measured in all animals in combination with either morphopathology or neurochemistry. By assessing these different measurements of brain function and structure in the same animal (with the exception of the neuropathology and neurochemistry which are incompatible), a more accurate and efficient evaluation of our hypotheses will be obtained. If our hypotheses prove correct, a new and rational therapeutic approach in the management of head injury patients may evolve.
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