Regulation of Cerebral Blood Flow After Traumatic Brain Injury

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The overall hypothesis of this proposal is that traumatic brain injury causes impairment of cerebral blood flow (CBF) regulation that produces a spectrum of injury in our head injured patients, ranging from frank ischemia to increased susceptibility to secondary insults. During the last grant period, we valuated a management strategy to prevent ischemia by providing the brain with a higher perfusion pressure that would compensate for the impaired ability of the injured brain to pressure autoregulate. This study demonstrated that we could significantly reduce the occurrence of secondary insults, but other consequences of the higher perfusion pressure (more adult respiratory distress syndrome, possibly worsened cerebral edema) offset the beneficial effects of reducing ischemic insults. The results of this study emphasize the importance of the proposed works. The overall goals of the proposed work are to develop methods for identifying those patients who are at greatest risk of secondary insults and to develop a way to prevent secondary cerebral ischemia by correcting the underlying vascular abnormalities that cause the injured brain to be sensitive to ischemic insults. The first overall goal will be achieved by studying CBF regulation in head injured patients and determining if abnormalities on these tests predict a greater risk of secondary insults (Specific Aims #1-2). At the end of the study, we plan to have identified simple tests that can be performed on admission to identify patients at greater risk from secondary insults and who therefore would benefit most from CBF-targeted therapy. The second goal will be achieved by studying the relationship of the myogenic response in isolated vessels to the impairment of autoregulation observed in vivo (Specific Aim #3), by studying the relationship of various vasoactive mediators to the impairment of CBF regulation observed in vivo (Specific Aim #3), and by studying the effect of L-arginine on CBF and on CBF regulation (Specific Aim #4). The specific aims include: 1. To develop practical methods for monitoring CBF regulation in the intensive care unit: 2. To study the incidence and severity of impairment of CBF regulation after TBI: 3. To study the cause of impairment of CBF regulation after TBI: 4. To study the effect of L-arginine on cerebral hemodynamics in patients with regional or global ischemia (CBF<20 ml/100gm/min) after TBI: