A brief history of spreading depolarization research

Human studies on spreading depolarization started in the late 1970s. Miron Sramka invasively recorded potassium induced spreading depolarizations in the human caudate nucleus and hippocampus. 

In the early 1980s, Olesen, Larsen and Lauritzen provided the first recordings of the normal neurovascular response to spreading depolarization in patients undergoing migraine aura. 

In the early 1990s, Avoli and colleagues provided first evidence of spreading depolarizations in human brain slices from patients with intractable epilepsy.

In the mid 1990s, Mayevsky and colleagues provided the first in vivo electrophysiological evidence of spreading depolarizations in one of 14 patients with traumatic brain injury using, a complex multiparametric monitoring system.

In the late nineties and early 2000s, significant increases in spreading depolarization velocity and susceptibility were found in mouse models of familial hemiplegic migraine type 1, a rare Mendelian model disease of migraine with aura. It was also observed that cerebral microangiopathies such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are associated with both higher incidence of migraine with aura in patients and higher susceptibility to spreading depolarization in animal models. Furthermore, inverse neurovascular coupling (spreading ischemia) was discovered – a mechanism that may underlie migrainous stroke and ischemic lesion progression.