| Objective Physical activities, including voluntary wheel running, have been shown to improve cognitive function in animal models and in patients with global cerebral ischemia. However, the neurochemical mechanisms of voluntary running on the global ischemic brain have not been well studied. The present study aims at the underlying neurochemical mechanism of hippocampal dopamine by observing cognitive improvement after global cerebral ischemia induced by pre-ischemia voluntary wheel running.Methods Sprague-Dawley(SD) rats were randomly divided into three groups including 4 weeks wheel running and 2-VO ischemia group(4W-I group,n=6), 1 week wheel running and 2-VO ischemia group(1W-I group,n=6), and 2-VO ischemia without wheel running group(I group,n=6). Ventral hippocampus microdialysis experiments were conducted in SD rats with 0, 1, or 4 weeks voluntary wheel running precondition. Microdialysate samples were collected from 30 min before ischemia to 70 min after ischemia. Dopamine levels in the microdialysate samples were detected by high performance liquid chromatography(HPLC) and electrochemical detection. Histological experiments were performed to evaluate ischemic neural cell injury in hippocampus. Additional rats were enrolled in this experiment to evaluate cognitive function after the global cerebral ischemia. All the additional rats were divided into the same groups and got the same exercise training as described above. Passive avoidance test was used to evaluate learning and memory ability after global cerebral ischemia.Results 1. The dopamine levels increased significantly in I group(P<0.001), which were induced by 2-VO ischemia, and reached to the peak at 20 min after ischemia, then decreased slightly at 70 min after ischemia. But the dopamine levels of 1W-I group and 4W-I group didn’t have any change significantly(P>0.05). 2. Compared with I group, the basal levels of hippocampal dopamine in 4W-I and 1W-I groups were significant increased(P<0.001). However, the basal levels have no difference between 4W-I and 1W-I groups(P>0.05). 3. In the behavioral experiment, the latency times in retention test of 4W-I and 1W-I groups were significant increased compared with I group(P<0.001). 4. Histological results showed that damaged hippocampal neural cells in I groupwere significant more than those in 4W-I and 1W-I groups.Conclusion These results suggest that global cerebral ischemia induces the release of hippocampal dopamine. This ischemia induced hippocampal dopamine increase can be inhibited by pre-ischemia voluntary wheel running. This inhabitation may be due to the voluntary wheel running induced increase of hippocampal dopamine basal level. |
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