Association of riluzole and dantrolene improves significant recovery after acute spinal cord injury in rats

Publication date: Available online 15 November 2017
Source:The Spine Journal
Author(s): Bernardo De Caro Martins, Bruno Benetti Junta Torres, Karen Maciel de Oliveira, Mario Sergio Lavor, Carla Maria Osório, Fabiola Bono Fukushima, Isabel Rodrigues Rosado, Eliane Gonçalves de Melo
Background ContextDamage to the spinal cord can result in irreversible impairment or complete loss of motor, sensory, and autonomic functions. Riluzole and dantrolene have been shown to provide neuroprotection by reducing neuronal apoptosis after brain and spinal cord injury (SCI) in several animal models of neurological disorders. As these drugs protect the injured spinal cord through different mechanisms, we investigated the cumulative effects of riluzole and dantrolene.PurposeThis study aimed to investigate the neuroprotective efficacy of the combined administration of riluzole and dantrolene in experimental thoracic SCI.Study DesignTwenty-nine Wistar rats were laminectomized at T12 and divided in five groups: Rats in GI (n=6) underwent laminectomy alone and were treated with placebo. Rats in GII (n=6) underwent laminectomy followed by SCI and were treated with placebo. Rats in GIII (n=5) underwent laminectomy followed by SCI and were treated with riluzole and placebo 15min and 1 h after laminectomy, respectively. Rats in GIV (n=6) underwent laminectomy followed by SCI and were treated with placebo and dantrolene 15min and 1 h after laminectomy, respectively. Rats in GV (n=6) underwent laminectomy followed by SCI and were treated with riluzole and dantrolene 15min and 1 h after laminectomy, respectively. A compressive trauma was performed to induce SCI.MethodsBehavioral testing of hindlimb function was performed using the Basso Beattie Bresnahan locomotor rating scale, which revealed significant recovery in the group treated with the association of riluzole and dantrolene compared to other groups. After euthanasia, the spinal cord was evaluated using light microscopy and immunochemistry with anti-NeuN and TUNEL staining.ResultsAnimals treated with the association of riluzole and dantrolene showed a larger number of NeuN-positive neurons adjacent to the epicenter of injury (P≤0.05). Furthermore, the TUNEL staining was similar between animals treated with riluzole and dantrolene and those that did not receive spinal cord trauma (P>0.05).ConclusionsThese results showed that riluzole and dantrolene have a synergistic effect in neuroprotection after traumatic SCI by decreasing apoptotic cell death.



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