title: Topiramate treatment is neuroprotective and reduces oligodendrocyte loss after cervical spinal cord injury.
abstract: Excess glutamate release and associated neurotoxicity contributes to cell death after spinal cord injury (SCI). Indeed, delayed administration of glutamate receptor antagonists after SCI in rodents improves tissue sparing and functional recovery. Despite their therapeutic potential, most glutamate receptor antagonists have detrimental side effects and have largely failed clinical trials. Topiramate is an AMPA-specific, glutamate receptor antagonists that is FDA-approved to treat CNS disorders. In the current study we tested whether topiramate treatment is neuroprotective after cervical contusion injury in rats. We report that topiramate, delivered 15-minutes after SCI, increases tissue sparing and preserves oligodendrocytes and neurons when compared to vehicle treatment. In addition, topiramate is more effective than the AMPA-receptor antagonist, NBQX. To the best of our knowledge, this is the first report documenting a neuroprotective effect of topiramate treatment after spinal cord injury.
authors.affiliation: Center for Brain and Spinal Cord Repair, Department of Neuroscience, The Ohio State University College of Medicine, Columbus, Ohio, United States of America. gensel.1@osu.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Gensel
authors.forename: C Amy
authors.initials: CA
authors.lastname: Tovar
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Bresnahan
authors.forename: Micheal S
authors.initials: MS
authors.lastname: Beattie
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002574:Cervical Vertebrae / Q000293:injuries*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006120:Grooming / Q000502:physiology; D006652:Histological Techniques; D009068:Movement / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D000077236:Topiramate
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011810:Quinoxalines; D000077236:Topiramate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D005632:Fructose