Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Whitehead, Shawn N.

2nd Supervisor

Sposato, Luciano A.

Co-Supervisor

Abstract

The neurological influence of ischemic stroke in the generation of stroke-induced heart injury (SIHI) has been acknowledged for several years. However, pathophysiological mechanisms remain uncertain. Clinically, it is hypothesized that stroke involving the insular cortex (IC) initiates SIHI, since the IC controls autonomic regulation of cardiovascular function. Yet, given the high prevalence of shared risk factors between ischemic stroke and cardiovascular disorders, mechanistic conclusions from clinical studies are largely speculative. We therefore sought to establish a novel rodent model of focal insular ischemic stroke, used to evaluate chronic outcomes of SIHI. Focal ischemic stroke was induced into the right or left IC of male Wistar rats, through stereotaxic injection of endothelin-1. Control groups received an injection of ibotenic acid, phosphate-buffered saline or no injection. Before euthanasia, rats were assessed for autonomic deficits in sensorimotor gating. At 28 days post-injection, rats with left IC damage displayed trends of impaired sensorimotor gating; compared to rats with right IC damage and control groups. Pathologically, all injured groups exhibited a chronic increase in microglia activation, present at the IC and remote white/grey matter regions. Furthermore, these groups expressed left atrial cardiac fibrosis. When correlated, a positive association between microglia activation and cardiac fibrosis was observed. With this novel model, we have identified several downstream consequences of IC ischemic stroke within the brain and heart; affirming the focal contribution of IC damage to SIHI. Taken together, these results provide insight into potential mechanisms of post-stroke cardiac damage, serving as future therapeutic targets for SIHI.

Available for download on Tuesday, December 31, 2019

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