Free radical scavenger edaravone produces robust neuroprotection in a rat model of spinal cord injury.

ABSTRACT

We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord injury (SCI). SCI was induced by extradural compression of thoracic spinal cord. In experiment 1, 30 min prior to compression, rats received a 3 mg/kg intravenous bolus of edaravone followed by a maintenance infusion of 1 (low-dose), 3 (moderate-dose), or 10 (high-dose) mg/kg/h edaravone. Although both moderate- and high-dose edaravone regimens promoted recovery of spinal motor-evoked potentials (MEPs) at 2 h post-SCI, the effect of the moderate dose was more pronounced. In experiment 2, moderate-dose edaravone was administered 30 min prior to compression, at the start of compression, or 10 min after decompression. Although both preemptive and coincident administration resulted in significantly improved spinal MEPs at 2 h post-SCI, the effect of preemptive administration was more pronounced. A moderate dose of edaravone resulted in significant attenuation of lipid peroxidation, as evidenced by lower concentrations of the free radical malonyldialdehyde in the spinal cord 3 h post-SCI. Malonyldialdehyde levels in the high-dose edaravone group were not reduced. Both moderate- and high-dose edaravone resulted in significant functional improvements, evidenced by better Basso-Beattie-Bresnahan (BBB) scores and better performance on an inclined plane during an 8 week period post-SCI. Both moderate- and high-dose edaravone significantly attenuated neuronal loss in the spinal cord at 8 weeks post-SCI, as evidenced by quantitative immunohistochemical analysis of NeuN-positive cells. In conclusion, early administration of a moderate dose of edaravone minimized the negative consequences of SCI and facilitated functional recovery.