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Neuroscience. 2019 Sep 1;415:1-9. doi: 10.1016/j.neuroscience.2019.07.006. Epub 2019 Jul 9.

Relief Following Chronic Stress Augments Spreading Depolarization Susceptibility in Familial Hemiplegic Migraine Mice.

Author information

1
Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
2
Department of Neurology Leiden University Medical Center, Leiden 2300, RC, the Netherlands; Human Genetics, Leiden University Medical Center, Leiden 2300, RC, the Netherlands.
3
Department of Neurology Leiden University Medical Center, Leiden 2300, RC, the Netherlands.
4
Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA; Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA. Electronic address: cayata@mgh.harvard.edu.

Abstract

Cortical spreading depolarization (CSD) is the electrophysiological substrate of migraine aura, and a putative trigger of trigeminovascular activation and migraine headache. Many migraineurs report stress or relief after a stress triggers an attack. We tested whether various stress conditions might modulate CSD susceptibility and whether this is dependent on genetic factors. Male and female wild type and familial hemiplegic migraine type1 (FHM1) knock-in mice heterozygous for the S218L missense mutation were subjected to acute or chronic stress, or chronic stress followed by relief (36 h). Acute stress was induced by restraint and exposure to bright light and white noise (3 h). Chronic stress was induced for 28 days by two cycles of repeated exposure of mice to a rat (7 days), physical restraint (3 days), and forced swimming (3 days). Electrical CSD threshold and KCl-induced (300 mM) CSD frequency were determined in occipital cortex in vivo at the end of each protocol. Relief after chronic stress reduced the electrical CSD threshold and increased the frequency of KCl-induced CSDs in FHM1 mutants only. Acute or chronic stress without relief did not affect CSD susceptibility in either strain. Stress status did not affect CSD propagation speed, duration or amplitude. In summary, relief after chronic stress, but not acute or chronic stress alone, augments CSD in genetically susceptible mice. Therefore, enhanced CSD susceptibility may explain why, in certain patients, migraine attacks typically occur during a period of stress relief such as weekends or holidays.

KEYWORDS:

FHM1; acute stress; chronic stress; cortical spreading depolarization; stress relief; weekend migraine

PMID:
31299346
PMCID:
PMC6731136
[Available on 2020-09-01]
DOI:
10.1016/j.neuroscience.2019.07.006

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