title: 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.
authors.affiliation: Department of Orthopaedic Surgery, Kyoto University, Kyoto City, Japan. sota@kuhp.kyoto-u.ac.jp
authors.forename: Souichi
authors.initials: S
authors.lastname: Ohta
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Iwashita
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kakinoki
authors.forename: Takashi
authors.initials: T
authors.lastname: Noguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine