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

作者：Martins Bernardo De Caro^*; Junta Torres Bruno Benetti; de Oliveira Karen Maciel; Lavor Mario Sergio; Osorio Carla Maria; Fukushima Fabiola Bono; Rosado Isabel Rodrigues; de Melo Eliane Goncalves

来源：Spine Journal, 2018, 18(3): 532-539.

DOI：10.1016/j.spinee.2017.10.067

• Clinical recovery
• Dantrolene
• Excitotoxicity inhibition
• Neuron preservation
• Riluzole
• Spinal cord injury

BACKGROUND CONTEXT: Damage 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 neurologic disorders. As these drugs protect the injured spinal cord through different mechanisms, we investigated the cumulative effects of riluzole and dantrolene.
PURPOSE: This study aimed to investigate the neuroprotective efficacy of the combined administration of riluzole and dantrolene in experimental thoracic SCI.
STUDY DESIGN: Twenty-nineWistar 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 15 minutes and 1 hour after laminectomy, respectively. Rats in GIV (n=6) underwent laminectomy followed by SCI and were treated with placebo and dantrolene 15 minutes and 1 hour after laminectomy, respectively. Rats in GV (n=6) underwent laminectomy followed by SCI and were treated with riluzole and dantrolene 15 minutes and 1 hour after laminectomy, respectively. A compressive trauma was performed to induce SCI.
METHODS: Behavioral testing of hind limb 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 with other groups. After euthanasia, the spinal cord was evaluated using light microscopy and immunochemistry with anti-NeuN and transferase dUTP nick-end-labeling (TUNEL) staining.
RESULTS: Animals treated with the association of riluzole and dantrolene showed a larger number of NeuN-positive neurons adjacent to the epicenter of injury (p <=.05). Furthermore, the TUNEL staining was similar between animals treated with riluzole and dantrolene and those that did not receive spinal cord trauma (p>.05).
CONCLUSIONS: These results showed that riluzole and dantrolene have a synergistic effect in neuroprotection after traumatic SCI by decreasing apoptotic cell death.

• 出版日期2018-3