Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (7): 1230-1236.doi: 10.4103/1673-5374.251330

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Early treadmill exercise increases macrophage migration inhibitory factor expression after cerebral ischemia/reperfusion

Min Cheol Chang 1 , Chae Ri Park 2 , Seung Hwa Rhie 3 , Woo Hyun Shim 2, 4 , Dae Yul Kim 3   

  1. 1 Department of Rehabilitation Medicine, College of Medicine, Yeungnam University, Daegu, Republic of Korea
    2 Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
    3 Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
    4 Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  • Online:2019-07-15 Published:2019-07-15
  • Contact: Dae Yul Kim, MD, dykimsmart@gmail.com.
  • Supported by:

    This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, No. 2016R1A2B4012772 (to DYK).

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Abstract:

The neuroprotective function of macrophage migration inhibitory factor (MIF) in ischemic stroke was rarely evaluated. This study aimed to investigate the effects of early treadmill exercise on recovery from ischemic stroke and to determine whether these effects are associated with the expression levels of MIF and brain-derived neurotrophic factor (BDNF) in the ischemic area. A total of 40 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group [middle cerebral artery occlusion (MCAO)-Ex, n = 10), ischemia and sedentary group (MCAO-St, n = 10), sham-surgery and exercise group (Sham-Ex, n = 10), or sham-surgery and sedentary group (Sham-St, n = 10). The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 minutes, whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO. Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 minutes once a day for 5 consecutive days. After reperfusion, the hanging time tested by the wire hang test was longer and the relative fractional anisotropy (rFA) determined by MRI was higher in the peri-infarct region of the MCAO-Ex group compared with the MCAO-St group. The expression levels of MIF and BDNF in the peri-infarct region were upregulated in the MCAO-Ex group. Increased MIF and BDNF levels were positively correlated with rFA changes in the peri-infarct region. There was no significant difference in the levels of MIF and BDNF in the peri-infarct region between the Sham-Ex and Sham-St groups. Our study demonstrated that early exercise (initiated 48 hours after the MCAO) could improve motor and neuronal recovery after ischemic stroke. Furthermore, the increased levels of MIF and BDNF in the peri-infarct region (penumbra) may be one of the mechanisms of enhanced neurological function recovery.

Key words: ischemic stroke, early exercise, macrophage migration inhibitory factor, brain-derived neurotrophic
factor, motor recovery, neural regeneration