The neuroprotective role of riluzole in spinal cord injury: a systematic review and meta-analysis

Eur J Trauma Emerg Surg. 2025 Jul 4;51(1):246. doi: 10.1007/s00068-025-02907-6.

Abstract

We systematically reviewed the evidence for the efficacy of riluzole on functional recovery and lesion size following spinal cord injury (SCI). The search was conducted on Medline, Embase, Scopus, and Web of Science by November 2024 for studies evaluating the utility of riluzole administration following SCI in rodents and humans. Neurological and histopathological outcomes were extracted for subjects treated and not treated with Riluzole. Pooled effect estimates were calculated using the random-effects model. Heterogeneity was assessed using the I2 and Chi2 tests. Fifteen preclinical studies were included. Meta-analysis demonstrated that riluzole significantly improves locomotion recovery (standardized mean difference (SMD) = 0.70; 95% confidence interval (CI): 0.46, 0.95; p < 0.0001; I2 = 0.00%) and subsides the lesion size (SMD = -1.74; 95% CI: -2.47 to -1.01; p < 0.0001; I2 = 55.84%). The improvement in locomotion was not significantly different between mild to moderate and severe injuries (meta-regression coefficient = -0.22; 95% CI: -0.74, 0.30; p = 0.403). Notably, riluzole significantly improves motor function and reduces lesion size in animals with acute traumatic SCI. The improvement only occurs with multi-dose administration of riluzole (SMD = 0.76; 95% CI: 0.49, 1.03; p < 0.0001), and no significant effect was observed with single-dose therapies (SMD = 0.49; 95% CI: -0.05, 1.02; p = 0.074). Most human studies also report motor function improvements, further suggesting riluzole's potential as a therapeutic agent in SCI. These findings support further research and trials to confirm its efficacy in clinical settings.

Keywords: Riluzole; Spinal cord injury; Trauma.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Animals
  • Humans
  • Locomotion / drug effects
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Recovery of Function / drug effects
  • Riluzole* / pharmacology
  • Riluzole* / therapeutic use
  • Spinal Cord Injuries* / drug therapy
  • Spinal Cord Injuries* / physiopathology

Substances

  • Neuroprotective Agents
  • Riluzole