title: Mechanically-induced cortical spreading depression associated regional cerebral blood flow changes are blocked by Na+ ion channel blockade.
abstract: Migraine with aura occurs in up to 20-30% of all migraineurs. The regional cerebral blood flow (rCBF) changes that occur during cortical spreading depression (CSD) are considered to be an experimental correlate of aura. CSD is synchronous with a failure in brain ion homeostasis and efflux of excitatory amino acids from nerve cells. Therefore studying the mechanisms that underlie CSD, such as ion channel manipulation, and observing rCBF changes may help our understanding of migraine aura. In this study we used mechanical stimulation to induce oligemia and hyperemia, in surgically prepared cats and rats, using laser Doppler probes to measure the cerebral blood flow and single cell cortical recording to measure the spike/neuronal burst, both generated as a consequence of CSD. We looked at the response of ion channel blockers directed at sodium, voltage-dependent calcium and ATP-activated potassium ion channels. The sodium ion channel blocker was able to inhibit rCBF changes in both the cat and rats. Voltage-dependent calcium channel blockers had little effect on the initiation or propagation of the spread, as did the ATP-activated potassium channel blocker. The data are consistent with what is known of human aura in that sodium ion channels are those predominantly involved in mechanical stimulation-induced rCBF changes and thus may represent therapeutic targets for the aura response in migraine.
authors.affiliation: Department of Neurology, University of California, San Francisco, 505 Parnassus Avenue, San Francisco CA 94143-0114, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Akerman
authors.forename: Philip R
authors.initials: PR
authors.lastname: Holland
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002415:Cats; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D013181:Cortical Spreading Depression / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006940:Hyperemia / Q000209:etiology / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin