The goal of my thesis was to elucidate the impact of protein-energy malnutrition (PEM, a condition commonly found in aging stroke patients) on outcomes from global ischemia. I first examined the hypothesis that PEM will impair working memory in the adult gerbil as measured in the T-maze. Gerbils were fed an adequate (12.5%) or low protein (2%; PEM) diet for 6wk. Stringent assessment of T-maze performance indicated an improvement with PEM although I was unable to reconcile whether this was increased motivation for the food reward or enhanced working memory.<p>
The second hypothesis tested was PEM will decrease expression of plasticity-associated hippocampal mRNA and protein expression following global ischemia in the gerbil. The plasticity markers brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (trkB), and growth-associated protein-43 (GAP-43) were examined in the CA1 hippocampal region post-ischemia. PEM induced in gerbils for 4wk did not alter the global ischemia-induced decrease in CA1 neurons. Ischemia resulted in increased CA1 pyramidal expression of BDNF and trkB mRNA at 1, 3, and 7d post-ischemia and increased trkB protein expression at 3 and 7d. PEM further elevated the increased trkB protein detected at 7d in the fibres. Ischemia resulted in increased GAP-43 protein at 3 and 7d post-ischemia with PEM increasing this expression at 3d in the CA3 and hilar regions in addition to CA1. These findings suggest an increased stress-response and/or hyperexcitability state in the hippocampus of malnourished ischemic animals.<p>
Since the reliability of the gerbil model of global ischemia has come into question, the third part of my thesis tested the hypothesis that the influence of pre-existing PEM on global ischemia-induced hippocampal injury can be reliably studied with the 2-vessel occlusion rat model. The impact of PEM on CA1 neuronal death and dendritic damage was examined. Rats received protein adequate (18%) or deficient (2%; PEM) diet for 7-8d prior to global ischemia. PEM did not worsen the decrease in CA1 neurons and dendrites observed at 7d post-ischemia. Importantly, I found that PEM altered blood glucose and acid-base balance during surgery and caused brief hypothermia post-surgically, factors which are important for consistent brain injury.<p>
Taken together, these findings reveal (i) that nutritional care, although frequently ignored, can have robust effects on recovery mechanisms after brain ischemia; and (ii) the challenges of studying pre-existing PEM in an established rodent model of stroke.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-09022010-094211 |
| Date | 27 September 2010 |
| Creators | Prosser-Loose, Erin Jane |
| Contributors | Paterson, Phyllis, Whiting, Susan, Verge, Valerie, Saucier, Deborah, Kalynchuk, Lisa, Harley, Carolyn |
| Publisher | University of Saskatchewan |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-09022010-094211/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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