Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (6): 1293-1299.doi: 10.4103/1673-5374.357900

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Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling 

Xin-Hong Jiang1, 2, 3, #, Hang-Feng Li4, #, Man-Li Chen2, 3, 5, Yi-Xian Zhang1, 2, 3, Hong-Bin Chen2, 3, 5, Rong-Hua Chen2, 3, 5, Ying-Chun Xiao2, 3, 5, Nan Liu1, 2, 3, 5, *#br#   

  1. 1Department of Rehabilitation, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China;  2Fujian Institute of Cerebrovascular Disease, Fuzhou, Fujian Province, China;  3Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian Province, China;  4Department of Neurology, Longyan First Hospital of Fujian Medical University, Longyan, Fujian Province, China;  5Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
  • Online:2023-06-15 Published:2023-01-05
  • Contact: Nan Liu, MD, xieheliunan1984@sina.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81772452 (to NL), the Fujian Province Joint Funds for the Innovation of Science and Technology, No. 2020Y9065 (to NL), Fujian Province Special Foundation for Natural Science Innovation Project, No. 2016B014  (to NL), and the Natural Science Foundation of Fujian Province, No. 2019J01160 (to XHJ).

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Abstract: Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia. However, whether there is a synergistic effect between the two remains unclear. In this study, we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes (MSC-exos) via the tail vein and underwent 14 successive days of treadmill exercise. Neurological assessment, histopathology, and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume, evident synaptic formation and axonal regeneration, and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment. These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone. Mechanistically, further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling. These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment, which may be related to activation of the JNK1/c-Jun signaling pathway. This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease. 

Key words: apoptosis, axonal regeneration, c-Jun, exosomes, functional remodeling, ischemic stroke, JNK1, mesenchymal stem cells, synaptic formation, treadmill exercise