Effects of Continuous Intravenous Infusion of MCI-186 on Functional Recovery after Spinal Cord Injury in Rats

Abstract

We investigated the effects of a free radical scavenger, MCI-186 (edaravone), on neuroprotection in the rat post-traumatic spinal cord using various doses and routes of administration. The injury was produced with a weight-drop device. Lipid peroxide formation in the spinal cord was measured using the thiobarbituric acid test for malonyldialdehyde (MDA). In the first experiment, MDA production in the untreated post-traumatic spinal cord reached peak values at 1 h post-trauma, and gradually decreased to control levels in 7 days. In the second experiment, rats received twice-daily injections (0, 1, 3, 5, 10, or 20 mg/kg) for 3 days. We found that 3 mg/kg was most effective functionally and histologically. In the third experiment, rats received a 3 mg/kg bolus + continuous infusion (0, 1.5, 2.4, or 3.0 mg/kg/h) for 1, 2, 4, and 8 h. We found that a 3 mg/kg bolus + infusion of 3.0 mg/kg/h was most effective for the inhibition of MDA production. In the fourth experiment, a 3 mg/kg bolus given once immediately after injury and twice daily for 3 days, a 3 mg/kg bolus + 3.0 mg/kg/h for 1 day, or a 3 mg/kg bolus + 3.0 mg/kg/h for 3 days were administered. The continuous infusion for 1 day showed significant improvement functionally and histologically, but continuous infusion at the same rate for another 2 days did not show any further improvement. To effectively reduce secondary neuronal damage, strong inhibition of free radical chain reactions at the early stage, particularly within the first 24 h post-trauma, is important.