LE3 .A278 2015

2015

Wilson, Brian

Acadia University

Bachelor of Science

Honours

Biology

Biology

Stroke is the third leading cause of death in Canada. At least two relaxin peptides are now known to protect heart, kidney, liver, pancreas, and brain tissues during ischemia through anti-inflammatory, vasodilatory, angiogenic, and anti-fibrotic actions. This makes relaxin a promising candidate as a stroke therapeutic. Previous work in our lab showed that in cultured brain slices exposed to oxygen and glucose-deprivation (OGD, mimicking conditions of ischemic stress), two relaxin peptides reduce cell death. Evidence also suggests that this protection may be mediated through a reduction in inflammation. Pro-inflammatory cytokines are signalling molecules that initiate the inflammatory response after ischemia. Therefore, it was my hypothesis that a relaxin peptide treatment would decrease cell death in cultured brain slices through a reduction of pro-inflammatory cytokines. To test this hypothesis, neonatal rat brains were sectioned, plated, and cultured for two weeks. Subsequently, slices were treated with one of three media conditions: normoxic glucose control, oxygen and glucose-deprived control, or oxygen glucose deprivation with one of three relaxin treatments (100 pM): human relaxin-2, human relaxin-3, or relaxin-3/insulin-5 (a relaxin-3receptor agonist). After treatment for 1 hour, slices were laced back into culture for 1 or 6 hours. Subsequently, slices were flash frozen and stored at -80° C. Protein was isolated and assayed for interleukin-1 beta and tumour necrosis factor alpha. Although relaxin peptides did not significantly reduce cytokine levels in OGD slices, the data suggest that relaxin-3 and relaxin-3/insulin-5 treatments may have reduced levels of the tested cytokines at a higher dosage. Further research is required to determine if relaxin peptides affect the release of pro-inflammatory cytokines in cultured brain tissue.

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