| Summary: | Thesis (M.Sc.)--Memorial University of Newfoundland 1996. Medicine Bibliography: leaves 60-77. It has been demonstrated that brief duration (e.g. 1.5-2 min) ischemia can provide neuroprotection against subsequent insults of longer duration. This phenomenon of ischemic tolerance or ischemic preconditioning was first reported in 1990 and has since received tremendous attention. The purpose of this investigation was to determine what effect ischemic preconditioning has on post-ischemic brain temperature, to assess whether histological preservation translates into functional protection and to observe whether there is a decline in neuroprotection with a longer survival time in a gerbil model of global ischemia. -- This study clearly demonstrated that preconditioning episodes of short duration ischemia provided significant histological protection of CA1 pyramidal cells against a subsequent ischemic insult that would typically produce roughly 95% necrosis of these neurons. Interestingly, histological protection in preconditioned ischemic animals did not result in concurrent behavioral protection. Preconditioned ischemic animals displayed a consistent habituation deficit when placed in the open field and were not different from untreated ischemic gerbils. A significant decline in CA1 preservation in preconditioned animals was observed when survival time was extended from 10 (81% protection) to 30 (53% protection) days. The lack of functional protection within the first 10 days postischemia, concomitant with the decline of cellular preservation over time suggests that this paradigm may not provide permanent protection if assessed at 2 or 3 months later. -- Consistent damage was observed in sector CA2 of the hippocampus in 21/22 preconditioned gerbils. Tolerance to ischemia failed to be induced in these neurons. In addition, several preconditioned animals displayed damage in the subiculum. Preconditioning ischemia did not affect the degree of hyperthermia observed following the lethal occlusion but did significantly reduce the duration of hyperthermia. However, this effect was small and thus ischemic preconditioning does not appear to be acting via a temperature mediated process. -- In light of the present findings, future research must be directed towards determining if the histological protection observed at 30 days is permanent or whether cell death would continue with longer survival times. Electrophysiological recording from CA1 would also help determine if these "preserved” CA1 neurons are fully functional. In the future the mechanisms of ischemic tolerance may be able to be activated pharmacologically thereby providing a novel therapy for the treatment of stroke.
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