Topiramate inhibits cortical spreading depression in rat and cat: impact in migraine aura.
Cortical spreading depression is thought to be the pathophysiological correlate of the neurological symptoms in migraine with aura. Topiramate is an anti-epileptic drug that is also used as a migraine preventive. Ion homeostasis and excitatory amino acid efflux are major components of cortical spreading depression; so given the broad range of actions of topiramate, we examined its effect on cortical spreading depression. Cortical spreading depression was elicited by a needle stick in the cortex in surgically prepared rats and cats; laser Doppler probes were used to measure the cerebral blood flow and a recording electrode was used to measure electrical nerve cell activity. Topiramate at 30 mg kg(-1) was able to inhibit regional cerebral blood flow changes and cortical depolarization and spreading depression in all rats, and in 8 of 13 cats. We conclude that topiramate may act on mechanisms involved in the initiation and propagation of spreading depression, and that these mechanisms may be similar to those involved in the therapeutic role.
Akerman
Simon
S
Headache Group, Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
Goadsby
Peter J
PJ
D000704:Analysis of Variance; D000818:Animals; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects*; D013181:Cortical Spreading Depression / Q000187:drug effects*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D009339:Needles / Q000009:adverse effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D000077236:Topiramate
D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose