Yongzhao Fan1, Yuhan Wang2, Wenliang Ji3, Kun Liu4, Hao Wu5. 1. Capital University of Physical Education and Sports, Beijing 100191, China. 2. Department of Pharmacology, the University of Tennessee College of Medicine Memphis, Tennessee 38163, United States. 3. Renmin University of China, Beijing 100872, China. 4. Capital University of Physical Education and Sports, Beijing 100191, China; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, United States. Electronic address: kunlukeliu@gmail.com. 5. Capital University of Physical Education and Sports, Beijing 100191, China. Electronic address: 626494696@qq.com.
Abstract
Cognitive impairment and anxiety are common health problems in acute ischemic stroke patients. Meanwhile, dopamine in the striatal brain region is significantly increased during the acute phase of cerebral ischemia. Besides, the studies shown that striatum and change of striatal dopamine are associated with learning and memory and anxiety. Further, physical exercise has been shown to improve neurocognitive and emotional function in animal models and patients with cerebral ischemia. However, the exact mechanism underlying this effect is unclear. The purpose of this research is to explore the effect of pre-ischemic voluntary wheel running on levels of striatal dopamine, cognition and anxiety in cerebral ischemia rats. METHODS: 48 adult male Sprague-Dawley rats were enrolled in this study and divided randomly in following 6 groups: sham group (S group, n = 8), ischemia group (I group, n = 8), 1 week wheel running group (1R group), 4 weeks wheel running group (4R group), 1 week pre-ischemia wheel running group (1RI group, n = 8) and 4 weeks pre-ischemia wheel running group (4RI group, n = 8). After training, cerebral ischemia was induced by permanent bilateral common carotid artery ligation (2-VO) operation. Microdialysis was used to collect dialysates from the striatum immediately from 30 min before ischemia to 90 min after ischemia. High-performance liquid chromatography-electrochemical detection system (HPLC) was used to determine the content of dopamine in the dialysates. Passive avoidance and elevated plus maze test were used to test neurocognitive function 24 h after 2-VO cerebral ischemia. RESULTS: As compare with the constant striatal dopamine level of S group, the striatal dopamine level in I group after ischemia showed a trend of rapid increasing and reached maximum value at the 20 min (P<0.001), then decreased gradually. The striatal dopamine level in 1RI and 4RI group showed the trend were similar to I group, but the increasing magnitude was attenuated. A comparison of the basal striatal dopamine level in 4 groups found that the basal dopamine level in 1RI and 4RI group were higher than S and I group (P<0.001). In passive avoidance task, the retention latency of I group was significantly shorter than S group (P<0.001), and the retention latency of the 1RI, 1R and 4R, 4RI group were longer than I group (P<0.001), there was no significant difference in S, 1RI, 1R, 4R and 4RI group (P>0.05). In elevated plus maze test, the time and entrance numbers of open arms in I group were significantly less than S group (P<0.05), but these indices were no significant difference in S, 1RI, 1R, 4RI and 4RI group. CONCLUSION: According to our results, 1 or 4 weeks pre-ischemia wheel running can significantly increase the basal dopamine level, attenuate the increase of striatal dopamine induced by cerebral ischemia and improve neurocognitive function in ischemia rats.
Cognitive impairment and anxiety are common health problems in acute ischemic strokepatients. Meanwhile, dopamine in the striatal brain region is significantly increased during the acute phase of cerebral ischemia. Besides, the studies shown that striatum and change of striatal dopamine are associated with learning and memory and anxiety. Further, physical exercise has been shown to improve neurocognitive and emotional function in animal models and patients with cerebral ischemia. However, the exact mechanism underlying this effect is unclear. The purpose of this research is to explore the effect of pre-ischemic voluntary wheel running on levels of striatal dopamine, cognition and anxiety in cerebral ischemiarats. METHODS: 48 adult male Sprague-Dawley rats were enrolled in this study and divided randomly in following 6 groups: sham group (S group, n = 8), ischemia group (I group, n = 8), 1 week wheel running group (1R group), 4 weeks wheel running group (4R group), 1 week pre-ischemia wheel running group (1RI group, n = 8) and 4 weeks pre-ischemia wheel running group (4RI group, n = 8). After training, cerebral ischemia was induced by permanent bilateral common carotid artery ligation (2-VO) operation. Microdialysis was used to collect dialysates from the striatum immediately from 30 min before ischemia to 90 min after ischemia. High-performance liquid chromatography-electrochemical detection system (HPLC) was used to determine the content of dopamine in the dialysates. Passive avoidance and elevated plus maze test were used to test neurocognitive function 24 h after 2-VOcerebral ischemia. RESULTS: As compare with the constant striatal dopamine level of S group, the striatal dopamine level in I group after ischemia showed a trend of rapid increasing and reached maximum value at the 20 min (P<0.001), then decreased gradually. The striatal dopamine level in 1RI and 4RI group showed the trend were similar to I group, but the increasing magnitude was attenuated. A comparison of the basal striatal dopamine level in 4 groups found that the basal dopamine level in 1RI and 4RI group were higher than S and I group (P<0.001). In passive avoidance task, the retention latency of I group was significantly shorter than S group (P<0.001), and the retention latency of the 1RI, 1R and 4R, 4RI group were longer than I group (P<0.001), there was no significant difference in S, 1RI, 1R, 4R and 4RI group (P>0.05). In elevated plus maze test, the time and entrance numbers of open arms in I group were significantly less than S group (P<0.05), but these indices were no significant difference in S, 1RI, 1R, 4RI and 4RI group. CONCLUSION: According to our results, 1 or 4 weeks pre-ischemia wheel running can significantly increase the basal dopamine level, attenuate the increase of striatal dopamine induced by cerebral ischemia and improve neurocognitive function in ischemiarats.