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Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta-analysis and systematic review

Zhou, L. Y. and Tian, Z. R. and Yao, M. and Chen, X. Q. and Song, Y. J. and Ye, J. and Yi, N. X. and Cui, X. J. and Wang, Y. J.

J Neurochem (2019) 150: 6–27

DOI: 10.1111/jnc.14686

Abstract

Spinal cord injury (SCI) is a devastating condition that has few treatment options. Riluzole, a sodium channel blocker used to treat amyotrophic lateral sclerosis, has been initially trialed in human SCI. We performed a systematic review to critically assess the efficacy of riluzole in locomotor recovery and damage extension in SCI rat models, and the potential for clinical translation. PubMed, Embase, Cochrane Library, and Chinese databases were searched from their inception date to March 2018. Two reviewers independently selected animal studies that evaluated neurological recovery and lesion area following riluzole treatment in SCI rat models, extracted data and assessed methodological quality. Pairwise meta-analysis, subgroup analysis, and network meta-analysis were performed to assess the effects of riluzole on SCI. Ten eligible studies were included. Two studies had high methodological quality. Overall, the Basso, Beattie, and Bresnahan scores were increased in riluzole-treated animals versus controls, and effect sizes showed a gradual increase from the 1st (five studies, n = 104, mean difference = 1.24, 95% CI = 0.11 to 2.37, p = 0.03) to 6th week after treatment (five studies, n = 120, mean difference = 2.34, 95% CI = 1.26 to 3.42, p \textless 0.0001). Riluzole was associated with improved outcomes in the inclined plane test and the tissue preservation area. Subgroup analyses suggested an association of locomotor recovery with riluzole dose. Network meta-analysis showed that 5 mg/kg riluzole exhibited greater protection than 2.5 and 8 mg/kg riluzole. Collectively, this review suggests that riluzole has a protective effect on SCI, with good safety and a clear mechanism of action and may be suitable for future clinical trials or applications. However, animal results should be interpreted with caution given the known limitations in animal experimental design and methodological quality.

Citation

Zhou, L. Y., Tian, Z. R., Yao, M., Chen, X. Q., Song, Y. J., Ye, J., Yi, N. X., Cui, X. J., & Wang, Y. J. (2019). Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta-analysis and systematic review. J Neurochem, 150(1), 6–27. https://doi.org/10.1111/jnc.14686 Animals, Rats, *meta-analysis, Recovery of Function/*drug effects, *spinal cord injury, Neuroprotective Agents/*pharmacology, *neurological function, *riluzole, *Spinal Cord Injuries/pathology, Riluzole/*pharmacology, Spinal Cord/*drug effects/pathology

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