Background and Objectives: Cerebral ischemia causes irreversible structural and functional damage in certain areas of the brain, especially in the hippocampus. The aim of this study was to examine effects of exercise preconditioning on neuronal cell death and expression of neurotrophin-4 (NT-4) and tropomyosin receptor kinase B (TrkB) in the hippocampal CA1 region following transient global cerebral ischemia/reperfusion in rat. Methods: Twenty-one male Wistar rats (weighing 250-300 g) were randomly divided into three groups (control+healthy, control+ischemia and exercise+ischemia). The rats in the exercise group ran on a treadmill five sessions a week for eight weeks. Ischemia was induced by occlusion of both common carotid arteries for 45 minutes. Cresyl violet staining was performed to assess cell death, and real-time PCR was carried out to evaluate expression of NT-4 and TrkB. Results: Cerebral ischemia was associated with significant neuronal death in the hippocampal CA1 region (P<0.05). Exercise significantly decreased the ischemia-induced cell death (P<0.05). NT-4 expression was significantly lower in the control+ischemia group and in the exercise+ischemia group compared to the control+healthy group (P<0.05), but there was no significant difference between the control+ischemia group and the exercise+ischemia group in terms of NT-4 expression (P˃0.05). Moreover, TrkB expression did not differ significantly between the groups (P˃0.05). Conclusion: When used as a preconditioning stimulant before the induction of cerebral ischemia, exercise could have neuroprotective effects against cerebral ischemia-induced cell death, but it has no significant effect on NT-4 and TrkB expression. h

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