Traumatic Brain Injury (tbi) Attenuates Arterial Smooth Muscle Vasorelaxation In Pressurized Cerebral Arteries

Abstract

Maintenance of cerebral blood flow (CBF) is impaired following traumatic brain injury (TBI), increasing the incidence of both ischemic and hemorrhagic events. Vascular tone is controlled by neurogenic, endothelial, and myogenic responses. PURPOSE: This work was designed to specifically determine the extent to which the myogenic response of vascular smooth muscle in the middle cerebral artery (MCA) is altered following TBI. METHODS: TBI was induced by controlled cortical impact (CCI) in 2-month-old male Sprague-Dawley rats. Twenty-four hours following injury or sham surgery, pressurized arterial myography was performed on endothelium-denuded MCA to examine the effect of TBI on smooth muscle-specific vasorelaxation using pharmacologic activators of the adenylyl cyclase (AC)-cAMP-PKA/PKG pathway (10-9M to 10-5M, n=6 at each dose). RESULTS: Myogenic tone was attenuated following TBI (25±1.1% vs. 18±1.2%, n=12; p<0.001). The mean change in myogenic tone in response to activators (10-6M) was reduced to 35% (AC), 33% (PKA), and 30% (PKG) in TBI as compared to sham controls. CONCLUSION: Attenuation of smooth muscle myogenic tone and resulting vasorelaxation following TBI may serve as a compensatory mechanism to protect sensitive brain tissue from cerebral ischemia. Future work will be needed to elucidate the role of pathways that could serve as potential targets for therapeutic intervention to reduce damaging vascular events. Supported by The Florida State University Graduate School Dissertation Award Grant.