Spreading depression as an innate antiseizure mechanism

Isra Tamim, David Y. Chung, Andreia Lopes Morais, Inge C. M. Loonen, Tao Qin, Amrit Misra, Frieder Schlunk, Matthias Endres, Steven J. Schiff and Cenk Ayata ()
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Isra Tamim: Massachusetts General Hospital, Harvard Medical School
David Y. Chung: Massachusetts General Hospital, Harvard Medical School
Andreia Lopes Morais: Massachusetts General Hospital, Harvard Medical School
Inge C. M. Loonen: Massachusetts General Hospital, Harvard Medical School
Tao Qin: Massachusetts General Hospital, Harvard Medical School
Amrit Misra: Department of Neurology, Massachusetts General Hospital, Harvard Medical School
Frieder Schlunk: Charité–Universitätsmedizin Berlin, Klinik und Hochschulambulanz für Neurologie und Centrum für Schlaganfallforschung Berlin (CSB)
Matthias Endres: Charité–Universitätsmedizin Berlin, Klinik und Hochschulambulanz für Neurologie und Centrum für Schlaganfallforschung Berlin (CSB)
Steven J. Schiff: The Pennsylvania State University
Cenk Ayata: Massachusetts General Hospital, Harvard Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22464-x

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