Autonomic Dysreflexia Impairs Cerebrovascular Health and Cognition in Experimental Spinal Cord Injury

Abstract

Autonomic dysreflexia (AD) is a life-threatening ephemeral episode of extreme hypertension occurring on a daily basis in the majority of individuals with high-level spinal cord injury (SCI). Although poorly controlled episodes of AD could lead to cerebral hemorrhage, the influence of chronic exposure to AD episodes on cerebrovascular function has never been explored. Furthermore, whether these transient elevations of blood pressure are beneficial or deleterious in chronically hypotensive individuals, such as those with SCI has been intensely debated. 14 days post complete T3 SCI rats were randomized to receive ether colorectal distension to induce AD (SCI+CRD n=7) or normal care (n=6). At 42 days post-SCI middle cerebral artery (MCA) structure and function was assessed ex vivo using pressure myography, and spatial acquisition and memory were assessed using Morris water maze. SCI+CRD rats exhibited reductions in MCA endothelium-dependent dilation assessed using carbachol (-36% at 10-5 M, P=0.04; Figure 1) and distensibility (-24% at 80 mmHg, P<0.0001). Myogenic tone was not different between groups. Additionally, spatial acquisition was impaired in SCI+CRD (i.e., +18% duration and distance to platform on day 4 training, both P=0.049). We demonstrate for the first time that chronic exposure to AD results in detrimental changes in cardiovascular health. Specifically, AD exposure was associated with impaired cerebrovascular function and cognitive deterioration in animals with SCI.