Author:
Kanbara Shunsuke,Ohkawara Bisei,Nakashima Hiroaki,Ohta Kyotaro,Koshimizu Hiroyuki,Inoue Taro,Tomita Hiroyuki,Ito Mikako,Masuda Akio,Ishiguro Naoki,Imagama Shiro,Ohno Kinji
Abstract
AbstractCervical spondylotic myelopathy (CSM) is caused by chronic compression of the spinal cord and is the most common cause of myelopathy in adults. No drug is currently available to mitigate CSM. Herein, we made a rat model of CSM by epidurally implanting an expanding water-absorbent polymer underneath the laminae compress the spinal cord. The CSM rats exhibited progressive motor impairments recapitulating human CSM. CSM rats had loss of spinal motor neurons, and increased lipid peroxidation in the spinal cord. Zonisamide (ZNS) is clinically used for epilepsy and Parkinson's disease. We previously reported that ZNS protected primary spinal motor neurons against oxidative stress. We thus examined the effects of ZNS on our rat CSM model. CSM rats with daily intragastric administration of 0.5% methylcellulose (n = 11) and ZNS (30 mg/kg/day) in 0.5% methylcellulose (n = 11). Oral administration of ZNS ameliorated the progression of motor impairments, spared the number of spinal motor neurons, and preserved myelination of the pyramidal tracts. In addition, ZNS increased gene expressions of cystine/glutamate exchange transporter (xCT) and metallothionein 2A in the spinal cord in CSM rats, and also in the primary astrocytes. ZNS increased the glutathione (GSH) level in the spinal motor neurons of CSM rats. ZNS potentially ameliorates loss of the spinal motor neurons and demyelination of the pyramidal tracts in patients with CSM.
Funder
Grants-in-Aids from the Japan Society for the Promotion of Science
Ministry of Health, Labour, and Welfare of Japan
Japan Agency for Medical Research and Development
Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP
Publisher
Springer Science and Business Media LLC
Cited by
10 articles.
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