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Relaxin, cerebral edema and the pathophysiology of stroke in rats

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dc.contributor.advisor Summerlee, Alastair Bergeron, Lindsay 2014-01-24T18:18:54Z 2014-01-24T18:18:54Z 2014-01 2014-01-16 2014-01-24
dc.description.abstract This thesis investigates the protective effects of relaxin peptides in ischemic stroke. Previous studies have shown that relaxin protects tissue from ischemic damage through initiation of multiple mechanisms, which may affect numerous pathophysiological events that are initiated after ischemic stroke. A relaxin paralog, relaxin-3, is found primarily in the central nervous system. The ability of relaxin-3 to provide protection to tissues under ischemic stress has not yet been explored although the abundant cerebral expression of this peptide and its native receptor make it a logical target for study. This thesis sets out to assess the protective effects upon relaxin peptide administration and aims to identify the mechanisms responsible for any observed protective effects using both in vitro and in vivo ischemic stroke models. The first set of experiments demonstrates that relaxin-3 is as effective in protecting the brain from the deleterious effects of ischemic stroke as is observed with relaxin treatment. These data also implicate cellular protection as a mechanism contributing to the overall defenses observed with relaxin treatment. The second set of experiments exhibit the ability of relaxin peptides to alter the myogenic reactivity of rat middle cerebral arteries. The ability of relaxins to modulate smooth muscle function may make these peptides promising candidates for vascular protection in ischemic stroke. Data from the third set of experiments suggest that relaxin peptides reduce the development of cytotoxic edema after ischemic stroke by modulating AQP4 levels on astrocyte foot processes in the peri-infarct area. Overall, this thesis presents protective mechanisms involved in the overall protection provided by relaxin administration. This research promises to increase our understanding of the role that relaxin peptides play in limiting damage to brain tissue during ischemia and raises an intriguing possibility for a therapeutic use of relaxin in ischemic stroke. en_US
dc.language.iso en en_US
dc.subject Stroke en_US
dc.subject Relaxin en_US
dc.subject Cardiovascular en_US
dc.subject Cerebral edema en_US
dc.title Relaxin, cerebral edema and the pathophysiology of stroke in rats en_US
dc.type Thesis en_US Biomedical Sciences en_US Doctor of Philosophy en_US Department of Biomedical Sciences en_US
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