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

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 < 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.

Muscone suppresses inflammatory responses and neuronal damage in a rat model of cervical spondylotic myelopathy by regulating Drp1‐dependent mitochondrial fission

“…Enhanced mitochondrial fission can cause mitochondrial dysfunction and further increase ROS generation (Yu, Sheu, Robotham, & Yoon, 2008). In the central nervous system (CNS), ROS derived from mitochondrial dysfunction may activate nuclear transcription factor‐κB (NF‐κB), mitogen‐activated protein kinase (MAPK), and/or the nod‐like receptor family, pyrin domain‐containing 3 (NLRP3) inflammasome to trigger activation of glial cells (Park et al, 2013; Wu et al, 2020; Zhou et al, 2019), and can also lead to neuronal damage through a wide range of mechanisms (Fan, He, et al, 2017; Wang, Yin, et al, 2017). Drp1‐dependent mitochondrial fission was proven to be highly associated with neuroinflammation and neuronal damage in CNS diseases (Katoh et al, 2017).…”

Do MTHFR C677T Genetic Polymorphism Influence in the Pathogenesis of Amyotrophic Lateral Sclerosis?

“…Nevertheless, studies report no signi cant increase in patient survival attributed to this drug treatment -only about two to three months [14,70]. Other medications are currently being studied for ALS treatment, such as Edaravone (Radicut), Masitinib [14], Tirasemtiv [71], and others. However, the progressive character of the disease and the lack of effective medication contribute to the short life expectancy after the diagnosis, which varies between three and ve years.…”

“…Riluzole is the only drug approved for ALS treatment in Brazil. Nevertheless, studies report no signi cant increase in patient survival attributed to this drug treatment -only about two to three months [14,70]. Other medications are currently being studied for ALS treatment, such as Edaravone (Radicut), Masitinib [14], Tirasemtiv [71], and others.…”

“…Riluzole, a glutamate antagonist, is currently the only medicine with proven e cacy in improving ALS survival, but it only increases life expectancy by two to three months. It is known that early diagnosis associated with drug therapy using riluzole may enhance its e cacy in clinical improvement [14,15].…”

Hippocampal hyperglutamatergic signaling matters: Early targeting glutamate neurotransmission as a preventive strategy in Alzheimer's disease

“…A high-affinity neuron-specific glutamine transport system inhibited by riluzole is described in developing and mature neuron-enriched hippocampal cultures (Erickson, 2017). Riluzole is approved by FDA for clinical use in patients with amyotrophic lateral sclerosis and is promising for spinal cord injury (both preclinical evidence, and clinical data are available) as a safe and well-tolerated neuroprotective treatment (Zhou et al, 2019). Riluzole is also discussed as a potential therapeutic drug for spinocerebellar ataxia type 3 (Schmidt et al, 2016).…”