Heterogeneous Mechanisms of Spreading Depolarization and Seizures

Abstract

Abstract Spreading depolarization (SD) is a massive, slowly migrating wave of near-complete cellular depolarization of neurons and glia associated with profound cytotoxic edema. SD is frequently generated following acute brain injury and contributes to the transient and chronic deterioration of neurological conditions. Clinical and basic studies also suggest that SD is a significant contributing mechanism of headache and neurological deficits in some migraine with aura. Because of the increasing evidence supporting the role of SD in these clinical conditions, there is a growing interest in exploring other neurological disorders that involve SD, including epilepsy. Both basic and clinical studies repeatedly demonstrate that seizure and SD can be co-generated in a temporally and spatially associated manner, suggesting the possibility that SD may be a comorbid feature of epilepsy. On the other hand, some studies suggest that the chronically epileptic brain is resistant to SD, and thus the relationship is still unclear. For technical reasons, clinical evidence of spontaneous SD generation in epilepsy and its interaction with seizures is very limited. Because mechanisms of SD and seizures can vary significantly in different contexts, their potential interaction likely requires individual evaluation depending on the type of epilepsy. This chapter will review the similarity and distinctions of molecular and physiological mechanisms of seizures and SD, and then discuss their clinical interaction in different pathological settings.