Background: The spinal cord is one of the central nervous system. Spinal cord injury (SCI) will cause loss of physical function and dysfunction below the injury site, causing them to lose sensation and mobility, thereby reducing the quality of life of patients. Although regular rehabilitation management can reduce its severity, the current effective treatment methods are limited to the treatment of secondary injuries to SCI. The purpose of treatment should not only include the restoration of the histology of the lesion, but also should focus on the restoration of sensory and mobility and. The key to effective treatment is to reduce secondary injuries. RhoA inhibitor can improve the pathophysiological changes related to secondary injury and promote the recovery of activity ability, so it may become a clinical drug for the treatment of SCI. This article systematically analyzed the effects of RhoA inhibitors on the promotion of axon regeneration and the recovery of mobility and compared the therapeutic effects of different inhibitors on SCI and their effects on physical function recovery.
Methods: We used a meta-analysis to systematically evaluate the effects of Rho inhibitors on SCI treatment and the recovery of body function.
Results: 21 articles (738 animals) were identified in the literatures search. Studies were selected if they reported the therapeutic effects of RhoA/ROCK inhibitors (BA-210, EGCG, β-elemene, C3-exoenzmye, LINGO-1-Fc, Ibuprofen, SiRhoA, iRhoA + FK506, Fasudil, p21Cip1/WAF1, HA-1007, Y-27,632 and C3bot154-182). We measure the functional recovery by BBB and BMS scores. The random effect model of weighted mean difference (WMD, 95 % confidence interval) was used to analyze the effects. The WMD of the forest graph was 2.277; 95 % CI: 1.705∼2.849, P < 0.001, suggesting that RhoA inhibitors can effectively treat SCI. In addition to EGCG, all the other agents also showed the effects on the activity recovery post-SCI (P < 0.05).
Conclusion: β-elemene, LINGO-1-Fc, Ibuprofen, SiRhoA, RhoA + FK506, Fasudil, p21Cip1/WAF1 and Y-27,632 have similar effects to BA-210, they can promote axon germination and nerve fiber regeneration after thoracic spinal cord injury and reduce the formation of syringomyelia and protect white matter, thereby improving locomotor recovery. RhoA inhibitors have great potential to restore motor function and provide a new trend for the treatment of SCI.
Keywords: Inhibitors; Locomotor function; Rho-associated kinase; Spinal cord injury.
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.