Comparative potency of sensory-induced brainstem activation to trigger spreading depression and seizures in the cortex of awake rats: Implications for the pathophysiology of migraine aura

Abstract

Background: Migraine and epilepsy are highly co-morbid neurological disorders associated with episodic dysfunction of both cortical and subcortical networks. The study examined the interrelation between cortical spreading depression, the electrophysiological correlate of migraine aura and seizures triggered at cortical and brainstem levels by repeated sound stimulation in rats with acoustic hypersensitivity (reflex audiogenic epilepsy).

Method: In awake, freely moving rats with innate audiogenic epilepsy, 25 episodes of running seizure (brainstem seizures) were induced by repeated sound stimulation. Spreading depression and seizures were recorded using implanted cortical electrodes.

Results: The first sound-induced brainstem seizures evoked neither spreading depression nor seizures in the cortex. With repetition, brainstem seizures began to be followed by a single cortical spreading depression wave and an epileptiform discharge. Spreading depression was more frequent an early cortical event than seizures: spreading depression appeared after 8.4 ± 1.0 repeated stimulations in 100% rats (n = 24) while cortical seizures were recorded after 12.9 ± 1.2 tests in 46% rats. Brainstem seizure triggered unilateral long-latency spreading depression. Bilateral short-latency cortical spreading depression was recorded only after intense cortical seizures.

Conclusion: These data show that episodic brainstem activation is a potent trigger of unilateral cortical spreading depression. Development of intense seizures in the cortex leads to initiation of spreading depression in multiple cortical sites of both hemispheres.

Keywords: Cortical spreading depression; animal models; brainstem; epilepsy; migraine; migraine aura.