Effects of exercise training on neurological recovery, TGF-β1, HIF-1α, and Nogo-NgR signaling pathways after spinal cord injury in rats

Xubin Ji, Zhaowan Xu, Dayong Liu, Yangwang Chen, Xubin Ji, Zhaowan Xu, Dayong Liu, Yangwang Chen

Abstract

Objective: To evaluate the effects of exercise training on neurological recovery, Growth Transforming Factor-β1 (TGF-β1), Hypoxia Inducible Factor-1α (HIF-1α), and Nogo-NgR signaling pathways after spinal cord injury in rats.

Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: normal group, sham-operated group, model group, and training group. The rat spinal cord injury model was established using Allen's method, and the training group received exercise training on the 8th day postoperatively. The Basso, Beattie and Bresnahan (BBB) score, modified Tarlow score, and inclined plane test scores were compared in each group before injury and 1, 7, 14, 21 and 28 days after injury.

Results: The BBB score and modified Tarlow score of the model group and the training group were 0 at the first day after the injury, and gradually increased on the seventh day onwards (p < 0.05). The BBB score and modified Tarlow score of the training group were higher than those of the model group at the 14th, 21st and 28th day (p < 0.05). The angles of the inclined plate at multiple time points after injury were lower in the model group and the training group than in the normal group and the sham-operated group (p < 0.05); The angles of the inclined plate at the 14th, 21st and 28th day after injury were higher in the training group than in the model group (p < 0.05).

Conclusion: The mechanism of exercise training may be connected to the inhibition of the Nogo-NgR signaling pathway to promote neuronal growth.

Keywords: HIF-1α; Motor training; Neurological function; Spinal cord injury; TGF-β1.

Conflict of interest statement

Conflicts of interest The authors declare no conflicts of interest.

Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.

Figures

Fig. 1
Fig. 1
Picture of experimental setup designed for the exercise training protocols in rats.
Fig. 2
Fig. 2
Observation of morphological changes of gastrocnemius muscle and spinal cord histology after spinal cord injury in rats using, HE staining. (A‒D) The morphological changes of gastrocnemius muscle in each group at 28 d after injury (A: normal group; B: sham-operated group; C: model group; D: training group). (E‒H) The morphological changes of spinal cord tissue in each group at 28 d after injury (E: normal group; F: sham-operated group; G: model group; H: training group).
Fig. 3
Fig. 3
Expression of TGF-β1 and HIF-1α in spinal cord tissue after spinal cord injury in rats. Fig. 3 shows that exercise training significantly reduced the expression of mRNA (A‒B) and protein (C‒D) of TGF-β1 and HIF-1α in spinal cord tissue after spinal cord injury. (E) shows the Western blot band images of TGF-β1 and HIF-1α protein expression. Note: Compared with the normal and sham-operated groups, ⁎⁎⁎p < 0.001; compared with model group, ###p < 0.001.
Fig. 4
Fig. 4
Expression of Nogo-NgR pathway in spinal cord tissue after spinal cord injury in rats. Fig. 4 shows that exercise training significantly reduced the expression of Nogo-A, NgR and LINGO-1 mRNA (A‒C) and protein (D‒F) in spinal cord tissue after spinal cord injury. G shows the Western blot band images of Nogo-NgR pathway protein expression. Note: Compared with the normal and sham-operated groups, ⁎⁎⁎p < 0.001; compared with model group, ###p < 0.001.

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