Dual role of spreading depolarization in an epileptic focus

Abstract Objective Spreading depolarizations (SDs) are often associated with epileptic discharges. Although SDs are traditionally thought to contribute to postictal depression and termination of epileptic discharges, seizures may also occur during SDs or may even follow SDs, suggesting that interactions between SD and seizures are more complex. Here, we examined the interactions between SD and epileptic activity by spatially separating the epileptic focus and the site of SD initiation. Methods Subdural electrocorticographic arrays (6 × 10 electrodes) and intracortical silicon probes were used to record SDs and epileptic activity in the rat parietal cortex. An epileptic focus was induced by local intracortical injection of the potassium channel blocker 4‐aminopyridine combined with the γ‐aminobutyric acid type A receptor antagonist gabazine, whereas extrinsic SDs were evoked by distal high‐potassium solution application. Results We found that extrinsic SDs exerted a biphasic effect; they initially promoted seizurelike events (SLEs) when the SD wave approached the epileptic focus, which was then followed by suppression of epileptic activity after the SD spread through the focus. The timing of SLEs relative to SDs varied at different recording sites, with SLEs occurring before, during, or after SD arrival depending on electrode position along the trajectory of SD propagation between the SD initiation site and the epileptic focus. During intracortical recordings, the proconvulsive effects of SD were associated with a wave of pre‐SD neuronal excitation reaching the epileptic focus. The epileptic focus per se also demonstrated resistance to the SD invasion. Significance The interactions between SDs and an epileptic focus are not limited to postictal depression, and SDs may also promote epileptic activity in the hyperexcitable cortex.