Spreading depolarization and its influence on epileptiform activity

Spreading depolarization (SD) is a transient disruption of electrographic activity that slowly propagates through the gray matter by chemical contiguity, and it is characterized by a large depolarization of neurons and glial cells. SD, which is associated with massive changes in ion homeostasis, including extreme increases in [K⁺]_o, was shown to occur in various neurological diseases such as migraine and traumatic brain injury. It is hypothesized to also occur in epilepsy. We review here the cellular and pharmacological features of SD that was mainly induced in vitro by different pharmacological manipulations as well as its relationship to focal seizures that can concomitantly occur in these in vitro and in vivo preparations. Recent experimental evidence points to SD playing a role in controlling seizure generation, but other studies have reported that SD facilitates ictogenesis. We conclude that further work is needed to firmly identify the role of SD in modulating focal seizure generation. These future experiments should also help in clearly defining the role played by SD in the manifestation of sudden unexpected death in epilepsy.