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Migraine mutations increase stroke vulnerability by facilitating ischemic depolarizations

Katharina Eikermann-Haerter1, Jeong Hyun Lee, Izumi Yuzawa

  • 1Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

Circulation
|December 7, 2011
PubMed
Abstract

Insights

Familial hemiplegic migraine (FHM) mutations increase stroke risk by making the brain more vulnerable to ischemic events. This heightened susceptibility to brain depolarization leads to larger strokes and worse outcomes.

Area of Science:

  • Neuroscience
  • Genetics
  • Stroke Research

Background:

  • Migraine is a known stroke risk factor, but underlying mechanisms remain unclear.
  • Familial hemiplegic migraine (FHM) serves as a valuable model for common migraine due to shared features and mechanisms.
  • FHM is associated with an increased risk of stroke.

Purpose of the Study:

  • To investigate the impact of FHM type 1 (FHM1) mutations on brain vulnerability to ischemic stroke.
  • To elucidate the cellular and physiological mechanisms linking FHM to stroke risk.

Main Methods:

  • Utilized two FHM1 mutant mouse strains and wild-type controls.
  • Assessed brain activity using anoxic depolarization and peri-infarct depolarizations.
  • Quantified infarct size and neurological outcomes using diffusion-weighted MRI and laser speckle flowmetry.
  • Investigated the effect of a glutamate receptor antagonist.

Main Results:

  • FHM1 mutations led to earlier anoxic depolarization and more frequent peri-infarct depolarizations in mutant mice.
  • Mutant mice exhibited rapid infarct core expansion and larger perfusion deficits.
  • Mutant mice required higher cerebral blood flow for survival, leading to infarction with milder ischemia.
  • Mutant mice developed larger infarcts and worse neurological outcomes, which were reduced by glutamate receptor antagonist treatment.

Conclusions:

  • Enhanced susceptibility to ischemic depolarizations, similar to spreading depression, predisposes migraineurs to infarction during mild ischemic events.
  • This mechanism contributes to the increased stroke risk observed in migraineurs.
  • Targeting glutamatergic mechanisms may offer therapeutic potential for stroke prevention in susceptible individuals.

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