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Migraine Prophylaxis, Ischemic Depolarizations, and Stroke Outcomes in Mice.
MedLine Citation:
PMID:  25424478     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression (SD) are implicated in the pathogenesis of both migraine and stroke. Spontaneous SD waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced SD susceptibility facilitates anoxic depolarizations and peri-infarct SDs and accelerates infarct growth, suggesting that susceptibility to SD is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses SD susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome.
METHODS: We measured the cortical susceptibility to SD and ischemic depolarizations, and determined tissue and neurological outcomes after middle cerebral artery occlusion in wild-type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing.
RESULTS: Chronic treatment with topiramate or lamotrigine reduced the susceptibility to KCl-induced or electric stimulation-induced SDs as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes were improved. Notably, treatment with a single dose of either drug was ineffective.
CONCLUSIONS: These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury.
Authors:
Katharina Eikermann-Haerter; Jeong Hyun Lee; Nilufer Yalcin; Esther S Yu; Ali Daneshmand; Ying Wei; Yi Zheng; Anil Can; Buse Sengul; Michel D Ferrari; Arn M J M van den Maagdenberg; Cenk Ayata
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-25
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  -     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-26     Completed Date:  -     Revised Date:  2014-11-27    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2014 American Heart Association, Inc.
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