Effects of anti-epileptic drugs on spreading depolarization-induced epileptiform activity in mouse hippocampal slices

Abstract

Epilepsy and spreading depolarization (SD) are both episodic brain disorders and often exist together in the same individual. In CA1 pyramidal neurons of mouse hippocampal slices, induction of SD evoked epileptiform activities, including the ictal-like bursts, which occurred during the repolarizing phase of SD, and the subsequent generation of paroxysmal depolarization shifts (PDSs), which are characterized by mild depolarization plateau with overriding spikes. The duration of the ictal-like activity was correlated with both the recovery time and the depolarization potential of SD, whereas the parameters of PDSs were not significantly correlated with the parameters of SD. Moreover, we systematically evaluated the effects of multiple anti-epileptic drugs (AEDs) on SD-induced epileptiform activity. Among the drugs that are known to inhibit voltage-gated sodium channels, carbamazepine, phenytoin, valproate, lamotrigine, and zonisamide reduced the frequency of PDSs and the overriding firing bursts in 20–25 min after the induction of SD. The GABA uptake inhibitor tiagabine exhibited moderate effects and partially limited the incidence of PDSs after SD. AEDs including gabapentin, levetiracetam, ethosuximide, felbamate, and vigabatrin, had no significant effect on SD-induced epileptic activity. Taken together, these results demonstrate the effects of AEDs on SD and the related epileptiform activity at the cellular level.

Cortical Spreading Depolarization in Chronic Subdural Hematoma: Bridging the Gap

“…The effect of LEV on CSD seems to be negligible in animal studies, whereas TPM has been shown to have an incisive effect on aborting CSD. 45 The study aims to show discrepancy in the evolution of patients in both groups, which would support the presence of a distinct etiology to epilepsy and the value of the NESIS score in detecting it while providing strengthening arguments supporting the statement that NESIS is the manifestation of CSD and providing evidence to potential therapeutic avenues and their potential prognostic impacts on patient outcomes.…”

Altered Spontaneous Glutamatergic and GABAergic Activity in the Peritumoral Cortex of Low-Grade Gliomas Presenting With History of Seizures

“…AEDs act through the suppression of voltage-gated sodium or calcium channels, potentiation of GABA, or inhibition of glutamate receptors ( Miziak et al, 2020 ). In in vitro mouse hippocampal slices, AEDs like carbamazepine, phenytoin, and valproate suppressed epileptiform discharges (paroxysmal depolarization shifts), but levetiracetam did not show any effect ( Lin et al, 2017 ). In vivo studies have also reported the modulation of neuronal activity due to AEDs.…”

Relationship between chronic hypoxia and seizure susceptibility

“…33 Lin, C.H., et al found that SD could induce epileptic activity in CA1 pyramidal neurons of mouse hippocampal slices, suggesting the involvement of SD induced by microglia activation in the increase in seizure susceptibility. 34 Therefore, chronic hypoxia can activate microglia to maintain SD susceptibility, induce neuroinflammation, release cytokines and chemokines, and activate downstream signaling pathways to establish a self-amplification cascade to improve neuronal excitability and increase seizure susceptibility.…”

“… 33 Lin, C.H., et al found that SD could induce epileptic activity in CA1 pyramidal neurons of mouse hippocampal slices, suggesting the involvement of SD induced by microglia activation in the increase in seizure susceptibility. 34 …”