EFFECTS OF SELENIUM ON SELENOPROTEINS AND BRAIN DAMAGE AFTER ISCHEMIA IN GERBILS
Date
2003-09
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Masters
Abstract
Increased oxidative stress is a major player in the cascade of events that cause cell death following a stroke. Since thioredoxin reductase (TrxR) and classical glutathione peroxidase (GPX1) are key elements of antioxidant defense, the experimental objective was to examine whether dietary Se influenced brain injury in global ischemia (I) by altering activity of these enzymes. Weanling male Mongolian gerbils were randomly assigned to 1 of 4 groups: 1) Se-deficient group (no Se added to the diet) subjected to ischemia [(-)SeI]; 2) Se-adequate group (0.2 mg Se/kg diet) and ischemia [(+)SeI]; 3) Se-adequate group and sham surgery [(+)SeS]; 4) Se-supplemented group (0.8 mg Se/kg diet) and ischemia [(+4-)SeI]. The influence of Se on brain TrxR and GPX1 activities following ischemia was investigated by studying groups 1-4. The effect of Se deficiency on ischemia-induced brain damage was examined by investigating groups 1 and 2. Global ischemia (5 minute occlusion of the common
carotid arteries with brain temperature at 36.5 ± 0.2 °C) or sham surgery followed 8-10 weeks of experimental diets. Liver, hippocampus, and neocortex were collected at 12 hours for biochemical analysis. For histological analysis, brains were fixed (10% buffered formalin) at 10 days post insult, embedded in paraffin, cut in 6µm sections, and stained with hematoxylin and eosin. The number of hippocampal CA1 neurons exhibiting distinct cell membranes and nuclei were counted in several sectors bilaterally, at 1.7, 2.2, and 2.7 mm posterior to Bregma. Se deficiency was confirmed in the (—)SeI group on the basis of liver GPX1 and TrxR activities being decreased to 5% and 67% of control values, respectively. TrxR was not upregulated in either brain region at 12 hours following ischemia, and this was confirmed in a separate experiment at 3 and 24 hours. GPX1 and TrxR activity in neocortex did not differ among groups. Se supplementation had no effect on hippocampal TrxR activity, while (-)SeI gerbils had significantly decreased TrxR activity relative to (+)SeI gerbils [mean ± SEM Units/mg protein; (-)SeI 9.4 ± 0.7 ; (+)SeI 12.4 ± 0.7]. Se deficiency did not increase hippocampal CAl damage in global ischemia, although the high variability in hippocampal damage hindered a definite conclusion. Future studies should reinvestigate the effect of decreased TrxR activity on inflammatory markers and brain damage at other timepoints postischemia.
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Degree
Master of Science (M.Sc.)
Department
Pharmacy and Nutrition