Spreading depression as an innate antiseizure mechanism

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

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish (US)
Article number2206
JournalNature communications
Issue number1
StatePublished - Dec 1 2021

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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