Mechanically-induced cortical spreading depression associated regional cerebral blood flow changes are blocked by Na+ ion channel blockade

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.