Spreading depolarization, a pathophysiological mechanism of stroke and migraine aura

Abstract

Spreading depolarization is a mechanism of abrupt, massive ion translocation between intraneuronal and extracellular space that entails cytotoxic edema in the brain’s gray matter. It is observed in patients as a large change of the slow electrical potential. Dependent on the energy status of the tissue, spreading depolarization is either preceded by nonspreading silencing due to neuronal hyperpolarization or accompanied by spreading silencing of electrical brain activity due to a depolarization block. Nonspreading silencing seems to translate into the initial clinical symptoms of ischemic stroke and spreading silencing translates into migraine aura. Direct electrophysiological evidence exists that spreading depolarization occurs in abundance in aneurysmal subarachnoid hemorrhage, delayed ischemic stroke after subarachnoid hemorrhage, malignant hemispheric stroke, spontaneous intracerebral hemorrhage and traumatic brain injury. Indirect evidence suggests its occurrence during migraine aura. In animals, spreading depolarizations facilitate neuronal death when they invade metabolically compromised tissue, whereas they are relatively innocuous in healthy tissue. Therapies targeting spreading depolarization may potentially treat these neurological conditions.