Interplay between Cortical Spreading Depolarization and Seizures

Abstract

Cortical spreading depolarization (CSD) is an electrophysiologic phenomenon found mostly in the setting of neurologic injury resulting in the disturbance of ion homeostasis and leading to changes in the local vascular response. The bioelectric etiology of CSD shares similarities to those in epileptic disorders, yet the relationship between seizures and CSD is unclear, with several studies observing cortical depression before, during, and after seizure activity, thus obscuring our understanding of whether CSD activity potentiates or limits seizures and vice versa. Cortical sampling has exhibited how the redistribution of ion concentrations in the intra- and extracellular environments interplay between the excitation of seizures and the electrical depression of CSD. Modeling of both environments has suggested that CSD synchronizes the affected tissue, creating a favorable environment for seizure activity; however, other studies have demonstrated the opposite: epileptiform activity initiating waves of CSD. Further studies have underscored the role of the vascular response and subsequent ischemia in CSD that contributes to epileptogenesis. Investigations in migraine, traumatic brain injury, and other neurologic injuries suggest that several drugs may target CSD. Manipulations in the occurrence and nature of CSD can potentially alter the threshold for seizure activity, and perhaps minimize immediate and long-term sequelae associated with epilepsy.

Understanding Spreading Depression from Headache to Sudden Unexpected Death

“…Conversely, stimulation-induced recurrent epileptiform discharges have been shown to block cortical and subcortical SD in rats ( 164 ). These findings do not allow a single interpretation of the interplay between SD and epilepsy, but they strongly suggest that there is a common mechanism in which a pivotal role may be played by NMDA receptors ( 165 ).…”

Characterization of Intrinsic Optical Signal during Spreading Depolarization

“…SD-induced spreading ischemia is so severe that it dramatically delays the energy-dependent recovery of SD and even leads to widespread necrosis of cortical neurons and astrocytes [4]. Experimental and clinical data has demonstrated that SD occurs abundantly after aneurysmal subarachnoid hemorrhage, intracerebral hemorrhage, traumatic brain injury, malignant hemispheric stroke, and epilepsy and plays an important role in secondary brain injury [5][6][7][8]. Moreover, SD is the pathophysiological substrate of migraine aura and a trigger for headache [9].…”

Segregation of seizures and spreading depolarization across cortical layers

“…6 Spreading depression was first described by Leão as a slowly propagating wave of complete cortical electrogram flattening following epileptic discharge evoked by tetanic electrical stimulation during alternate current (AC) electroencephalographic (EEG) recordings. 6 Spreading depression was first described by Leão as a slowly propagating wave of complete cortical electrogram flattening following epileptic discharge evoked by tetanic electrical stimulation during alternate current (AC) electroencephalographic (EEG) recordings.…”

“…Various factors promoting SD (high potassium, low magnesium, enhanced synaptic activity, glutamate receptor agonists) also promote seizures and moreover, seizures and SD frequently co-occur in various experimental models and patients. 6 Spreading depression was first described by Leão as a slowly propagating wave of complete cortical electrogram flattening following epileptic discharge evoked by tetanic electrical stimulation during alternate current (AC) electroencephalographic (EEG) recordings. 7 Large negative shifts were later described during SD 8 using full-band direct current (DC)-coupled recordings, which are now considered the gold standard for SD detection.…”