The potential role of RhoA/ROCK-inhibition on locomotor recovery after spinal cord injury: a systematic review of in-vivo studies.

STUDY DESIGN

Systematic Review.

OBJECTIVES

To thoroughly assess the existing literature regarding the impact of anti-RhoA/ROCK agents or procedures on functional recovery in animal models of SCI.

SETTING

Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences.

METHODS

A comprehensive search was conducted in Ovid MEDLINE, Embase, Scopus, and Web of Science Core Collection utilizing a combination of keywords. All in-vivo animal studies of acute or chronic SCI that evaluated the pharmacological effects of Rho/ROCK inhibitors in English literature were included in this study.

RESULTS

Totally, 2320 articles were identified, of which, 60 papers were included for further analysis. A total of 47 (78%) studies were conducted merely on rats, 9 (15%) on mice, 3 (5%) used both, and the remaining used other animals. Y-27632, Fasudil, C3 Transferase and its derivatives (C-05/PEP-C/CT04/Cbot154-182/Cbot26mer(156-181)), Ibuprofen, Electroacupuncture (EA), SiRhoA, miR-133b, miR-135-5p, miR-381, miR-30b, Statins, 17β-estradiol, β-elemene, Lentivirus-mediated PGC-1a, Repulsive guidance molecule (RGMa), Local profound hypothermia, Jisuikang (JSK), Hyperbaric oxygen (HBO), Lv-shRhoA (Notch-1 inhibitor), Anti-Ryk antibody, LINGO-antagonist, BA-210, p21Cip1/WAF1, ORL-1 antagonist, Epigallocatechin-3-gallate (EGCG), Tamsulosin, AAV.ULK1.DN, and Indomethacin were the 28 reported agents/procedures with anti-RhoA/ROCK effects. The pooled SMD for BBB scores was 0.41 (p = 0.048) in the first week, 0.85 (p < 0.001) in the second week, 1.22 (p = 0.010) in the third week, and 1.53 (p = 0.001) in the fourth week.

CONCLUSION

Of the 28 identified anti-RhoA/ROCK agents, all but two (Cbot and its derivatives and EGCG) demonstrated promising results. The results of the meta-analysis cautiously indicate a significant increase in BBB scores over time after SCI.