Neuroprotection and enhanced recovery with edaravone after acute spinal cord injury in rats.
METHODS
The effect of edaravone, a novel free radical scavenger, was assessed functionally and histologically using a rat spinal cord contusion model.


OBJECTIVE
To investigate the effect of edaravone on neuroprotection after spinal cord injury in rats.


BACKGROUND
The spinal cord injury results in immediate physical damage (primary injury), followed by a prolonged neural tissue disorder (secondary injury). This secondary injury process has been suggested to be induced by lipid peroxidation. Edaravone has been reported to inhibit lipid peroxidation in cerebral ischemia models.


METHODS
Spinal cord injury at the T10 level was induced with a weight drop device (10 g weight, 25 mm height). Edaravone was administered intravenously as a bolus dose of 5 mg/kg at 5 minutes, 24 hours, and 48 hours after injury (edaravone-treated rats). In control rats, nothing was administered. Functional assessment was conducted weekly using the Basso-Beattie-Bresnahan locomotor rating scores. Histologically, a percentage of spared white matter area was calculated. The effects of intravenous administration of edaravone on lipid peroxide formation in rat spinal cord homogenate were examined using the thiobarbituric acid test for malonyldialdehyde production.


RESULTS
Six weeks after injury, edaravone-treated rats showed significantly higher motor score and larger spared white matter area than control rats. The administration of edaravone attenuated malonyldialdehyde production in spinal cord homogenate by >45%.


CONCLUSIONS
Edaravone enhanced functional recovery and preserved more spinal cord tissue after spinal cord injury in rats. The attenuation of posttraumatic lipid peroxide formation by edaravone partially contributed to this enhancement.
Ohta
Souichi
S
Department of Orthopaedic Surgery, Kyoto University, Kyoto, Japan. sota@ea.mbn.or.jp
Iwashita
Yasushi
Y
Takada
Hideaki
H
Kuno
Sadako
S
Nakamura
Takashi
T
D000208:Acute Disease; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D007275:Injections, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; D000077553:Edaravone; D000983:Antipyrine