This application lists specific aims intended to examine the neurogenic control of the cerebral circulation by studying the effects of both vessel deafferentation and electrical trigeminal stimulation on feline cerebral blood flow, pial vessel caliber and permeability using the radiolabeled microspheres, pial window technique, and albumin tracers. Previous studies have identified the presence of vasodilating and permeability promoting peptides (substance P, neurokinin A, calcitonin gene-related peptide) within trigeminal nerve fibers innervating cephalic blood vessels, and have shown that with depolarization, these peptides become released into the walls of cephalic blood vessels. In preliminary experiments, we demonstrated an enhanced and sustained ipsilateral vasoconstrictor response to topical norepinephrine in both small and large pial blood vessels following trigeminal ganglionectomy (less than .1), and less vasodilation and plasma protein extravasation on the side ipsiilateral to the lesion during severe forced hypertension (less than .05). We propose to expand these observations by measuring and comparing cerebral blood flow in the intact and lesioned sides and by determining whether there are indeed sided differences in blood flow and pial vessel diameter with severe hypertension or hypotension, hyper- or hypocarbia, hypoxia, head injury, seizures, or the infusion of vasoconstrictor substances into the subarachnoid space. Cerebral blood flow and pial diameters will also be measured during unilateral trigeminal ganglion stimulation in normal animals and after rhizotomy to determine whether the antidromic release of vasodilation peptides can cause vasodilation of pial blood vessels. By so doing, we hope to better understand mechanisms of vasodilation and to further explore neurogenic control of the cerebral circulation in health and disease.
