Document Detail


Migraine mutations increase stroke vulnerability by facilitating ischemic depolarizations.
MedLine Citation:
PMID:  22144569     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Migraine is an independent risk factor for stroke. Mechanisms underlying this association are unclear. Familial hemiplegic migraine (FHM), a migraine subtype that also carries an increased stroke risk, is a useful model for common migraine phenotypes because of shared aura and headache features, trigger factors, and underlying glutamatergic mechanisms.
METHODS AND RESULTS: Here, we show that FHM type 1 (FHM1) mutations in Ca(V)2.1 voltage-gated Ca(2+) channels render the brain more vulnerable to ischemic stroke. Compared with wild-type mice, 2 FHM1 mutant mouse strains developed earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations associated with rapid expansion of infarct core on diffusion-weighted magnetic resonance imaging and larger perfusion deficits on laser speckle flowmetry. Cerebral blood flow required for tissue survival was higher in the mutants, leading to infarction with milder ischemia. As a result, mutants developed larger infarcts and worse neurological outcomes after stroke, which were selectively attenuated by a glutamate receptor antagonist.
CONCLUSIONS: We propose that enhanced susceptibility to ischemic depolarizations akin to spreading depression predisposes migraineurs to infarction during mild ischemic events, thereby increasing the stroke risk.
Authors:
Katharina Eikermann-Haerter; Jeong Hyun Lee; Izumi Yuzawa; Christina H Liu; Zhipeng Zhou; Hwa Kyoung Shin; Yi Zheng; Tao Qin; Tobias Kurth; Christian Waeber; Michel D Ferrari; Arn M J M van den Maagdenberg; Michael A Moskowitz; Cenk Ayata
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-05
Journal Detail:
Title:  Circulation     Volume:  125     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-17     Completed Date:  2012-04-12     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  335-45     Citation Subset:  AIM; IM    
Copyright Information:
© 2011 American Heart Association, Inc.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain Ischemia / physiopathology*
Calcium Channels, N-Type / genetics
Cerebrovascular Circulation
Cortical Spreading Depression
Disease Susceptibility
Magnetic Resonance Imaging
Mice
Migraine Disorders / complications,  genetics*
Migraine with Aura / genetics
Mutation*
Stroke / etiology*,  genetics
Grant Support
ID/Acronym/Agency:
DA024235/DA/NIDA NIH HHS; DA026108/DA/NIDA NIH HHS; NS055104/NS/NINDS NIH HHS; NS057556/NS/NINDS NIH HHS; NS061505/NS/NINDS NIH HHS; NS35611/NS/NINDS NIH HHS; P01 NS035611-04/NS/NINDS NIH HHS; P01 NS035611-04S1/NS/NINDS NIH HHS; P01 NS035611-05/NS/NINDS NIH HHS; P01 NS035611-06/NS/NINDS NIH HHS; P01 NS035611-07/NS/NINDS NIH HHS; P01 NS035611-08/NS/NINDS NIH HHS; P01 NS035611-09/NS/NINDS NIH HHS; P01 NS035611-10/NS/NINDS NIH HHS; P01 NS035611-11A1/NS/NINDS NIH HHS; P01 NS035611-12/NS/NINDS NIH HHS; P01 NS035611-13/NS/NINDS NIH HHS; P01 NS035611-14/NS/NINDS NIH HHS; P01 NS035611-15/NS/NINDS NIH HHS; R01 NS061505/NS/NINDS NIH HHS; R01 NS061505-01/NS/NINDS NIH HHS; R01 NS061505-02/NS/NINDS NIH HHS; R01 NS061505-03/NS/NINDS NIH HHS; R01 NS061505-04/NS/NINDS NIH HHS; R01 NS061505-05/NS/NINDS NIH HHS; R21 DA024235/DA/NIDA NIH HHS; R21 DA024235-01/DA/NIDA NIH HHS; UL1 RR025758/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Calcium Channels, N-Type; 0/voltage-dependent calcium channel (P-Q type)
Comments/Corrections

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