Author: Ito, H.; Wate, R.; Zhang, J.; Ohnishi, S.; Kaneko, S.; Ito, H.; Nakano, S.; Kusaka, H.
Description: Edaravone is a free-radical scavenger, an agent being widely used for cerebral ischemia in Japan. To evaluate its efficacy for possible treatment of amyotrophic lateral sclerosis (ALS), we performed a randomized blind trial in ALS model mice. After identification of the clinical onset in each female G93A mutant SOD1 transgenic mouse, we intraperitoneally administered multiple doses of edaravone to the mice and observed their motor symptoms. We also counted the number of lumbar motoneurons, determined the 3-nitrotyrosine/tyrosine ratio, and evaluated the abnormal SOD1 aggregation in the spinal cord at the 10th day after the edaravone injection. Edaravone significantly slowed the motor decline of the transgenic mice. The remaining motoneurons were significantly preserved in the higher-dose edaravone-administered group, and the 3-nitrotyrosine/tyrosine ratios were reduced dose-dependently. Intriguingly, the area of abnormal SOD1 deposition in the spinal cord was significantly decreased in the higher-dose edaravone-administered group. Our results indicate that edaravone was effective to slow symptom progression and motor neuron degeneration in the ALS model mice. These favorable actions might be attributable to the yet unidentified mechanism responsible for reducing the deposition of mutant SOD1.
Subject headings: Amyotrophic Lateral Sclerosis/drug therapy/enzymology; Animals; Antipyrine/administration & dosage/analogs & derivatives; Female; Humans; Male; Mice; Mice, Transgenic; Motor Skills/drug effects/physiology; Motor Skills Disorders/drug therapy/enzymology; Superoxide Dismutase/genetics/metabolism; Superoxide Dismutase-1; Time Factors
Publication year: 2008
Journal or book title: Experimental Neurology
Volume: 213
Issue: 2
Pages: 448-455
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Type: Journal Article
Serial number: 1838