Water Treadmill Training Ameliorates Neurite Outgrowth Inhibition Associated With NGR/RhoA/ROCK by Inhibiting Astrocyte Activation Following Spinal Cord Injury

Background: Axons become scattered and incomplete after spinal cord injury (SCI). Cross-talk between astrocytes and neurons plays a pivotal role in neurite outgrowth following SCI. Rehabilitative training is a recognized method for the treatment of SCI, but the specific mechanism of its effect on axonal outgrowth in the central nervous system (CNS) has not been determined. Methods: : A total of 160 adult male SD rats weighing 200–250 g were randomly divided into three groups, and an SCI animal model was established. Rats were subjected to water treadmill training (TT) for 7 or 14 d. The Basso-Beattie-Bresnahan (BBB) motor function scale, hematoxylin-eosin (HE) staining, Nissl staining, Western blotting and immunofluorescence were used to measure the degree of neurological deficit, tissue morphology, quantitative expression and accurate localization of the corresponding proteins. Results: : We found that TT decreased tissue structure damage and improved functional recovery. TT promoted the regeneration of neurons and reduced apoptosis induced by SCI around the lesion. TT significantly increased the expression of GAP43 and NF200 after SCI. In addition, the injury-induced increase in the expression of proinflammatory factors was significantly inhibited by TT. TT reduced the activation of astrocytes and microglia, accompanied by reduced expression of C3d and higher increased of S100A10. Finally, the level of chondroitin sulfate proteoglycan (CSPG) surrounding the lesion and activation of the NGR/RhoA/ROCK signalling pathway in neurons after SCI were effectively inhibited by TT. Conclusions: : In this study, we found that TT played a novel role in recovery from SCI by promoting axonal outgrowth associated with the NGR/RhoA/ROCK by inhibiting astrocyte activation after SCI.