Grant: CIHR Fellowship

While paralysis is commonly viewed as the most devastating consequence of spinal cord injury (SCI), a major under-appreciated issue is cognitive impairment which occurs due to dysfunction of brain blood vessels. Impaired cognition drastically impacts the rehabilitation process, social integration and overall quality of life. My recently published study shows that up to 60% of individuals with SCI have impaired cognition and thus highlights the seriousness of this issue. Long term high blood pressure, in otherwise healthy individuals is known to damage blood vessels in the brain and cause cognitive impairment. Strikingly, majority of people with a high-level SCI suffer from a life-threatening condition called autonomic dysreflexia, where daily activities such as a bowel routine trigger extreme uncontrolled spikes in blood pressure up to 40 times per day. These spikes in blood pressures go up to 300mmHg- well above brain's maximum tolerable limit of 150mmHg, To study this, we have developed a rat model of SCI that shows blood pressure dysfunction similar to humans and also significant cognitive decline post injury. First, we will use this model to thoroughly understand how extreme blood pressure fluctuations cause brain damage resulting in cognitive decline. Second, the main reason behind blood pressure dysregulation is loss of crucial regulatory pathways brainstem after SCI. We will reconnect those lost pathways using a nerve bridge and enzymatic treatment of injury scar. Our preliminary studies show that the nerve bridge significantly improves blood pressure control. We predict that this treatment approach will improve brain health and cognitive function following SCI. Therapies based on nerve transplantation are already in safety trials in humans with SCI. Understanding its implications in blood pressure control and cognitive function can help address these issues, which are of higher patient priority that walking but are unfortunately, understudied.