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Background: Spreading depolarization (SD), underlying mechanism of migraine aura and potential activator of pain pathways, is known to elicit transient local silencing cortical activity. Sweeping across the cortex, the electrocorticographic depression is supposed to underlie spreading negative symptoms of migraine aura. Main information about the suppressive effect of SD on cortical oscillations was obtained in anesthetized animals while ictal recordings in conscious patients failed to detect EEG depression during migraine aura. Here, we investigate the suppressive effect of SD on spontaneous cortical activity in awake animals and examine whether the anesthesia modifies the SD effect., Methods: Spectral and spatiotemporal characteristics of spontaneous cortical activity following a single unilateral SD elicited by amygdala pinprick were analyzed in awake freely behaving rats and after induction of urethane anesthesia., Results: In wakefulness, SD transiently suppressed cortical oscillations in all frequency bands except delta. Slow delta activity did not decline its power during SD and even increased it afterwards; high-frequency gamma oscillations showed the strongest and longest depression under awake conditions. Unexpectedly, gamma power reduced not only during SD invasion the recording cortical sites but also when SD occupied distant subcortical/cortical areas. Contralateral cortex not invaded by SD also showed transient depression of gamma activity in awake animals. Introduction of general anesthesia modified the pattern of SD-induced depression: SD evoked the strongest cessation of slow delta activity, milder suppression of fast oscillations and no distant changes in gamma activity., Conclusion: Slow and fast cortical oscillations differ in their vulnerability to SD influence, especially in wakefulness. In the conscious brain, SD produces stronger and spatially broader depression of fast cortical oscillations than slow ones. The frequency-specific effects of SD on cortical activity of awake brain may underlie some previously unexplained clinical features of migraine aura., (© 2024. The Author(s).)

Functional connectivity analysis is gaining more interest due to its promising clinical applications. To study network mechanisms underlying seizure termination and postictal depression, we explore dynamics of interhemispheric functional connectivity near the offset of focal and bilateral seizures in the experimental model of reflex audiogenic epilepsy. In the model, seizures and spreading depression are induced by sound stimulation of genetically predisposed rodents. We characterize temporal evolution of seizure-associated coupling dynamics in the frontoparietal cortex during late ictal, immediate postictal and interictal resting states, using two measures applied to local field potentials recorded in awake epileptic rats. Signals were analyzed with mean phase coherence index in delta (1-4 Hz), theta (4-10 Hz) beta (10-25 Hz) and gamma (25-50 Hz) frequency bands and mutual information function. The study shows that reflex seizures elicit highly dynamic changes in interhemispheric functional coupling with seizure-, region- and frequency-specific patterns of increased and decreased connectivity during late ictal and immediate postictal periods. Also, secondary generalization of recurrent seizures (kindling) is associated with pronounced alterations in resting-state functional connectivity - an early wideband decrease and a subsequent beta-gamma increase. The findings show that intracortical functional connectivity is dynamically modified in response to seizures on short and long timescales, suggesting the existence of activity-dependent plastic network alterations that may promote or prevent seizure propagation within the cortex and underlie postictal behavioral impairments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cortical spreading depolarization (CSD) is the neuronal correlate of migraine aura and the reliable consequence of acute brain injury. The role of CSD in triggering headaches that follow migraine aura and brain injury remains to be uncertain. We examined whether a single CSD occurring in awake animals modified the expression of proinflammatory cytokines (Il1b, TNF, and Il6) and endogenous mediators of nociception/neuroinflammation-pannexin 1 (Panx1) channel and calcitonin gene-related peptide (CGRP), transforming growth factor beta (TGFb) in the cortex. Unilateral microinjury of the somatosensory cortex triggering a single CSD was produced in awake Wistar rats. Three hours later, tissue samples from the lesioned cortex, intact ipsilesional cortex invaded by CSD, and homologous areas of the contralateral sham-treated cortex were harvested and analyzed using qPCR. Three hours post-injury, intact CSD-exposed cortexes increased TNF, Il1b, Panx1, and CGRP mRNA levels. The strongest upregulation of proinflammatory cytokines was observed at the injury site, while CGRP and Panx1 were upregulated more strongly in the intact cortexes invaded by CSD. A single CSD is sufficient to produce low-grade parenchymal neuroinflammation with simultaneous overexpression of Panx1 and CGRP. The CSD-induced molecular changes may contribute to pathogenic mechanisms of migraine pain and post-injury headache.

Introduction: K + channels are of great interest to epilepsy research as mutations in their genes are found in humans with inherited epilepsy. At the level of cellular physiology, K+ channels control neuronal intrinsic excitability and are the main contributors to membrane repolarization of active neurons. Recently, a genetically modified voltage-dependent K + channel has been patented as a remedy for epileptic seizures., Areas Covered: We review the role of potassium channels in excitability, clinical and experimental evidence for the association of potassium channelopathies with epilepsy, the targeting of K+ channels by drugs, and perspectives of gene therapy in epilepsy with the expression of extra K+ channels in the brain., Expert Opinion: Control over K+ conductance is of great potential benefit for the treatment of epilepsy. Nowadays, gene therapy affecting K+ channels is one of the most promising approaches to treat pharmacoresistant focal epilepsy.

Mixed forms of epilepsy in patients are often refractory. Therefore, animal models of comorbid convulsive and nonconvulsive seizure are needed for experimental research. Susceptibility to audiogenic convulsions was studied in a large group of young and adult WAG/Rij rats with inherited absence epilepsy. In 30% of adult rats, sound stimulation provoked audiogenic seizures of moderate intensity. The seizures had two excitation periods separated by a remarkably stable "arrest" of paroxysmal movements. Up to 20% of young WAG/Rij rats were also susceptible to audiogenic seizures, with a longer latency, lower intensity, and more simple seizure patterns. No difference in manifestations of spike-wave discharges was observed between the WAG/Rij rats with and without audiogenic seizures. This subpopulation of WAG/Rij rats genetically predisposed to absence and audiogenic seizures is proposed as an animal model suitable for investigation of basal mechanisms and pharmacological profiles of this mixed form of epilepsy.

Subconvulsive dosages (40 mg/kg) of intraperitoneally applied pentylenetetrazol (PTZ) elicit, after a latency of 1 min, slow potential waves of spreading depression (SD) in the thalamus and 20 s later also in the cerebral cortex of rats. The PTZ-induced SD waves appear only exceptionally in the caudate nucleus and hippocampus. Repeated daily application of 40 mg/kg PTZ elicits kindling of epileptic phenomena manifested by increasing incidence of high-amplitude spikes in the EEG, myoclonic jerks and minimal and later maximal generalized seizures but by decreasing incidence of cortical SD. It is concluded that kindled epileptic activity interferes with the generation of SD waves the reduced incidence of which may contribute to the development of more severe forms of epilepsy.