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Journal of Integrative Neuroscience  2019, Vol. 18 Issue (1): 65-70    DOI: 10.31083/j.jin.2019.01.118
Original Research Previous articles | Next articles
Voluntary exercise promotes neurotrophic factor and suppresses apoptosis in hippocampal ischemia
Zhixiong Zhang1, #, Rong Li1, #, Xiaoyan Zhang1, Yaxuan Wei1, Hongbing Ma1, Ling Zhu1, Rong Yin1, *()
1Department of Neurology, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, No.333 Binhe Road, Qilihe District, Lanzhou City, Gansu Province, 730050, China
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Previous studies have demonstrated that exercise facilitates recovery from ischemia. However, the mechanisms need to be further elucidated. The current investigation was designed to study the effect of voluntary exercise on cerebral ischemia and discuss possible mechanisms usingmiddle cerebral artery occlusion model. Rats were randomly allocated to three groups: control, middle cerebral artery occlusion, and middle cerebral artery occlusion plus exercise. The middle cerebral artery occlusion plus exercise group was preconditioned by three weeks of voluntary wheel running prior to surgery. The accelerated rotarod test was employed to evaluate motor performance. Infarct volumes were analyzed to detect the neuroprotective effect of voluntary exercise. Brain-derived neurotrophic factor, Bax, Bcl-2, and caspase-3 protein expressions were measured by Western blot. Behavior evaluation showed the middle cerebral artery occlusion plus exercise group achieved significantly longer time on a rotarod than the unexercised group. Additionally, voluntary exercise reduced cerebral infarction and increased brain derived neurotrophic factor expression. Exercise down-regulated the apoptotic Bax/Bcl-2 ratio and caspase-3 protein expression. Results indicate that voluntary wheel running promote hippocampal brain derived neurotrophic factor and inhibit cell apoptosis in ischemia-induced impairment.

Key words:  Hippocampal ischemia      voluntary exercise      brain-derived neurotrophic factor      apoptosis      rodent     
Submitted:  24 December 2018      Accepted:  15 March 2019      Published:  30 March 2019     
  • 18QNP053/Youth Development Program of PLA
  • 1506RJZA302/Gansu Natural Science Fund Project
*Corresponding Author(s):  Rong Yin     E-mail:
# These authors contribute equally.

Cite this article: 

Zhixiong Zhang, Rong Li, Xiaoyan Zhang, Yaxuan Wei, Hongbing Ma, Ling Zhu, Rong Yin. Voluntary exercise promotes neurotrophic factor and suppresses apoptosis in hippocampal ischemia. Journal of Integrative Neuroscience, 2019, 18(1): 65-70.

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Figure 1.  Rotarod test showing behavioral and motor functional analyses. The latency of falling from the rotarod was recorded at 7, 14, and 21 days post surgery (n = 8). Data presented as mean $\pm$ SEM. *** p < 0.00 vs. control group; $\sharp$ p < 0.05 vs. MCAO group.

Figure 2.  Effect of exercise on cerebral infarct volume in MCAO rats. Cerebral infarct volumes in the MCAO group were significantly higher, while exercise preconditioning significantly reduced cerebral infarct volumes (n = 4). Data presented as mean $\pm$ SEM. ** p < 0.01 vs. control group; $\sharp\sharp$ p < 0.01 vs. MCAO group.

Figure 3.  Protective effect of exercise on MCAO-induced down-regulation of BDNF. (A) Western blot showing BDNF expression. (B) Quantification of BDNF expression by Western blot (n = 3). Data presented as mean $\pm$ SEM. ** p < 0.01 vs. control group; $\sharp\sharp$ p < 0.01 vs. MCAO group.

Figure 4.  Effect of exercise on expression of Bax, Bcl-2, and caspase-3. (A) Effect of MCAO and exercise on Bcl-2 and Bax expression. (B) Western blot showing Bax expression (n = 3). (C) Western blot showing Bcl-2 expression (n = 3). (D) Exercise profoundly inhibited the construction-mediated up-regulation of the Bax/Bcl-2 ratio. (E) Western blot showing caspase-3 expression. (F) Quantification of caspase-3 expression by Western blot (n = 3). Data presented as mean $\pm$ SEM. * p < 0.05 vs. control group; ** p < 0.01 vs. control group; *** p < 0.001 vs. control group; $\sharp$ p < 0.05 vs. MCAO group; $\sharp\sharp$ p < 0.01 vs. MCAO group, $\sharp\sharp\sharp$ p < 0.001 vs. MCAO group.

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