Hyperleptinemia increases the susceptibility of the cortex to generate cortical spreading depression.

BACKGROUND: Obesity is a risk factor for episodic migraine to develop into chronic migraine; hence, it is speculated that obesity and hyperleptinemia are associated with migraine. We hypothesized that leptin is involved in the mechanisms of cortical spreading depression (CSD). Therefore, we examined whether leptin affected a rat model of CSD to clarify the relationship between leptin and migraine. METHODS: We evaluated the effect of intracerebroventricular (ICV) administration of leptin on a rat CSD model. We then examined whether once-a-day intraperitoneal administration of leptin for seven days (as a chronic hyperleptinemia model) affected rat CSD models. Finally, we induced CSD in Zucker fatty (ZF) rats, which is a well-known model of obesity. RESULTS: In the parietal cortex, the percent change in cerebral blood flow and direct current (DC) potential decreased after ICV administration of leptin. A similar decrease in DC potential was observed in rats treated with intraperitoneal leptin. The number of CSDs increased significantly in rats given intraperitoneal leptin and in ZF rats. CONCLUSIONS: The present study suggests that leptin is involved in the mechanisms of CSD.