Primary brain injury in stroke is followed by oxidative stress and further neural damage. Glutathione (GSH) is critical in antioxidant
defense. Since cysteine is limiting in GSH synthesis, Phase 1 of this study investigated the effect of a dietary sulphur amino acid deficiency (-SAA) on neural damage in global hemispheric hypoxia-ischemia (GHHI). Rats were fed a -SAA or control diet for 6 days, and subjected to GHHI after 3 days. Histologically evaluated neural damage at 7 days post hypoxia-ischemia was greater in -SAA rats. Brain GSH concentration was decreased in -SAA rats 3 days after ischemia. A cysteine precursor, L-2-oxothiazolidine-4-carboxylic acid (OTC) administered to -SAA rats did not ameliorate neural damage. GSH is decreased by protein-energy malnutrition (PEM) in some tissues. Phase 2 investigated the effect of PEM on brain oxidative stress, neural damage and behaviour after global ischemia in adult male gerbils. In a 2x2 factorial design, gerbils were fed an adequate protein (12%; C) or low protein (2%; PEM) diet for 4 weeks, then subjected to transient ischemia (I) or sham surgery (S). After 12 hours of reperfusion, brain from half the gerbils was collected for biochemical analyses. Remaining gerbils were fed pre-surgery diets for 10 more days. To assess functional consequences of ischemia, gerbils were placed in an open field on Days 3, 7 and 10 after surgery. On Day 10, viable hippocampal CA1 neurons were counted. C-I gerbils did not habituate as readily in the open field on day 3 as C-S, but normalized by day 7. PEM-I gerbils failed to habituate by day 10, traveled greater distance than other gerbils and 7 of 12 displayed thigmotaxis, a <i>wall-hugging</i> preference for the outer perimeter of the open field. CA1 neuron loss in I was 61.5% of S, but unaffected by PEM. Four of 12 PEM-I gerbils had marked increases in hippocampal glia. Hippocampus protein thiols were reduced by PEM and by ischemia, consistent with oxidative stress. GSH concentration, glutathione reductase activity and thiobarbituric acid reactive substances were not significantly affected by PEM or ischemia. Findings from these two studies suggest well-nourished but not nutritionally-deficient rodents tolerate a mild brain insult. This is clinically relevant because many elderly stroke victims suffer from PEM at the time of ischemia, which may compromise recovery.
| Identifer | oai:union.ndltd.org:USASK/oai:usask.ca:etd-10312003-133029 |
| Date | 31 October 2003 |
| Creators | Bobyn, Patricia Joan |
| Contributors | Whiting, Susan J., Saucier, Deborah M., Paterson, Phyllis G., Juurlink, Bernhard H. J., Hamilton, Donald L., Bray, Tammy M., Zello, Gordon A. |
| Publisher | University of Saskatchewan |
| Source Sets | University of Saskatchewan Library |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-10312003-133029/ |
| 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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