1. Academic Validation
  2. Treadmill exercise improves neurological function by inhibiting autophagy and the binding of HMGB1 to Beclin1 in MCAO juvenile rats

Treadmill exercise improves neurological function by inhibiting autophagy and the binding of HMGB1 to Beclin1 in MCAO juvenile rats

  • Life Sci. 2020 Feb 15;243:117279. doi: 10.1016/j.lfs.2020.117279.
Guoyuan Pan 1 Lingqin Jin 1 Weimin Shen 1 Jieqiong Zhang 1 Juanjuan Pan 1 Jingyan Cheng 1 Qingfeng Xie 1 Quan Hu 1 Shamin Wu 1 Hongmei Zhang 2 Xiang Chen 3
Affiliations

Affiliations

  • 1 Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou, Zhejiang, China.
  • 2 Hangzhou Children's Hospital, 195 Wenhui Road, Hangzhou, Zhejiang, China. Electronic address: [email protected].
  • 3 Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou, Zhejiang, China. Electronic address: [email protected].
Abstract

Aims: Treadmill exercise is a beneficial treatment following childhood stroke. Thus, studies focusing on the neuroprotective mechanism of exercise training during postischemic treatment in children with ischemic stroke are urgently needed. We evaluated the effects of treadmill exercise on Autophagy after cerebral ischemia in young rats.

Main methods: Rats (23-25 days old) underwent cerebral ischemia-reperfusion (CI/R) surgery. The experimental Animals were divided into 5 groups, and some groups received either treadmill exercise, a rapamycin (RAPA) injection or combination therapy for 3 or 7 days. We performed a series of experimental tests including neurological scoring, hematoxylin-eosin staining (H&E), Nissl staining, triphenyl tetrazolium chloride (TTC) staining, Western blot analysis (WB), immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and Terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) fluorescence.

Key findings: The experimental data indicated that treadmill exercise inhibited Autophagy in the ischemic penumbra, inhibited high mobility group box 1 (HMGB1) translocation and binding to Beclin1, reduced Apoptosis, reduced infarct volumes, and aided in functional recovery. However, RAPA promoted the opposite effects of treadmill exercise.

Significance: We found that treadmill exercise improves the neurological deficits induced by CI/R by inhibiting Autophagy and HMGB1 binding to Beclin1.

Keywords

Autophagy; Childhood stroke; HMGB1; Treadmill exercise.

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