Our specific aims are to demonstrate that a) disturbances in the cerebral microcirculation, unrelated to vasospasm, develop after subarachnoid hemorrhage (SAH) resulting in global reductions of cerebral blood flow (CBF) and metabolism; b) these disturbances are indicative of a disorder in cerebrovascular autoregulation, perhaps contributing to delayed cerebral ischemia; c) these global alterations of CBF and metabolism are induced by hyperactivity of the noradrenergic neurons derived from the locus coeruleus (LC), which projects diffusely to all regions of the central nervous system and have profound effects on regional cerebral metabolism, CBF, vascular permeability, and cerebral autoregulation. Changes in CBF, metabolic activity, cerebrovascular autoregulation, and brain norepinephrine will be quantitated following experimental SAH in rats. These results will be compared in animals with and without prior destruction of the LC. CBF and metabolism will be studied in these animals using a 14C-butanol indicator fractionation technique, and 14C-deoxyglucose autoradiography. Brain tissue catecholamines will be analyzed with a radioenzymatic assay. These studies might be significant in delineating pathophysiological contributions to cerebral ischemia after SAH. The results might suggest new approaches to patients with ruptured intracranial aneurysms.
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