LE3 .A278 2013

2013

Wilson, Brian

Acadia University

Bachelor of Science

Honours

Biology

Biology

In humans, relaxins are a group of 3 peptide hormones within the insulin peptide superfamily. The main circulating form of relaxin (H2 relaxin) has been shown to reduce the cellular damage associated with ischemia – a lack of oxygen resulting from decreased perfusion – in tissues of organs including the heart, intestine and pancreas. Previous results from our lab have shown that H2 relaxin protects brain tissue from ischemic damage. This study investigated the effects of relaxin-3 (H3 relaxin), a relaxin neuropeptide, on damage to the brain during ischemia and reperfusion as well as an examination of the role of nitric oxide (NO) as a mediator. The study was performed in vitro using brain slices from the brains of 10-11 day old neonatal rats. Slices were exposed to one of seven possible treatments: baseline, control, oxygen and glucose deprived (OGD), OGD with H2 relaxin, OGD with H2 relaxin and a blocker of inducible nitric oxide Synthase (iNOS), OGD with H3 relaxin and OGD with H3 relaxin and an blocker of iNOS. Propidium iodide (PI) fluorescence was used to quantify the number of dead cells in the slices. H2 relaxin and H3 relaxin-treated slices had significantly reduced numbers of PI positive, cells compared to untreated slices. Blockade of iNOS significantly attenuated the effect of both relaxins. These data suggest that both H2 and H3 are neuroprotective and that NO mediates this effect, at least in part. Overall, these findings show that H3 relaxin is neuroprotective in rat brain tissue under ischemic stress. These findings are the first to demonstrate this. Ultimately, the application of these data may lead to a better understanding of relaxin physiology in the brain and point towards clinical use of these peptides in patients who suffer strokes.

The author retains copyright in this thesis. Any substantial copying or any other actions that exceed fair dealing or other exceptions in the Copyright Act require the permission of the author.

https://scholar.acadiau.ca/islandora/object/theses:991