CALCITONIN-GENE-RELATED PEPTIDE REDUCES BRAIN INJURY IN A RAT MODEL OF FOCAL CEREBRAL-ISCHEMIA

Background and Purpose Calcitonin gene-related peptide is an endogenous vasodilating neuropeptide with a dense concentration in the trigeminocerebrovascular system. It is hypothesized that depletion of this peptide contributes to delayed cerebral ischemia after subarachnoid hemorrhage and that an exogenous supply of calcitonin gene-related peptide will augment ischemic cerebral blood flow and reduce neuronal injury. Methods In this study we have investigated the effect of an intravenous infusion of calcitonin gene-related peptide (100 ng/kg per minute), started 1 hour before and continued throughout 4 hours of focal cerebral ischemia, on cerebral blood flow and the volume of brain injury in a rat model of middle cerebral artery occlusion. Results Calcitonin gene-related peptide produces a significant improvement in ischemic cerebral blood flow (32+/-2 compared with 13+/-2 mL/100 g per minute in the controls; t=6.92 P<.0001) with a concomitant reduction in the volume of ischemic brain injury (102+/-22 compared with 234+/-19 mm(3); t=4.47, P<.001). Conclusions These findings lend support for the potential use of this peptide in the prophylactic treatment of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.