Spreading Depression As an Innate Antiseizure Mechanism

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Apr 14

PMID 33850125

Citations 28

Authors

Isra Tamim

David Y Chung

Andreia Lopes de Morais

Inge C M Loonen

Tao Qin

Amrit Misra

Frieder Schlunk

Matthias Endres

Steven J Schiff

Cenk Ayata

Affiliations

Soon will be listed here.

Abstract

Spreading depression (SD) is an intense and prolonged depolarization in the central nervous systems from insect to man. It is implicated in neurological disorders such as migraine and brain injury. Here, using an in vivo mouse model of focal neocortical seizures, we show that SD may be a fundamental defense against seizures. Seizures induced by topical 4-aminopyridine, penicillin or bicuculline, or systemic kainic acid, culminated in SDs at a variable rate. Greater seizure power and area of recruitment predicted SD. Once triggered, SD immediately suppressed the seizure. Optogenetic or KCl-induced SDs had similar antiseizure effect sustained for more than 30 min. Conversely, pharmacologically inhibiting SD occurrence during a focal seizure facilitated seizure generalization. Altogether, our data indicate that seizures trigger SD, which then terminates the seizure and prevents its generalization.

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