Suppressive effect of chronic peroral topiramate on potassium-induced cortical spreading depression in rats

Objective: To evaluate the chronic effect of topiramate (TPM) on cortical spreading depression (CSD), which is thought to be related to migraine aura.Methods: Male rats (n = 30) were randomized to once-daily peroral treatment with TPM (50, 100, 200 or 600 mg/kg) or vehicle for 6 weeks. We evaluated the characteristics of CSD induced by topical application of KCl under isoflurane anesthesia and the changes in plasma level of TPM in each group. The effect of single administration of TPM on CSD was also evaluated.Results: After the final administration of TPM, when the plasma level of TPM was high, KCl-induced CSD frequency and CSD propagation velocity were dose-dependently reduced and the interval between CSD episodes was elongated, compared with the vehicle control. However, before the final administration of TPM, when the plasma level was very low, the KCl-induced CSD profile was the same as that in the vehicle control. Single administration of TPM did not alter the CSD profile. Local cerebral blood flow was not significantly altered by chronic administration of TPM.Conclusion: TPM suppressed the frequency and propagation of CSD along the cerebral cortex, and might be a candidate for relief of migraine.