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Aura and Stroke: relationship and what we have learnt from preclinical models
BACKGROUND: Population-based studies have highlighted a close relationship between migraine and stroke. Migraine, especially with aura, is a risk factor for both ischemic and hemorrhagic stroke. Interestingly, stroke risk is highest for migraineurs who are young and otherwise healthy. MAIN BODY: Pre...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Milan
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734247/ https://www.ncbi.nlm.nih.gov/pubmed/31142262 http://dx.doi.org/10.1186/s10194-019-1016-x |
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author | Yemisci, Muge Eikermann-Haerter, Katharina |
author_facet | Yemisci, Muge Eikermann-Haerter, Katharina |
author_sort | Yemisci, Muge |
collection | PubMed |
description | BACKGROUND: Population-based studies have highlighted a close relationship between migraine and stroke. Migraine, especially with aura, is a risk factor for both ischemic and hemorrhagic stroke. Interestingly, stroke risk is highest for migraineurs who are young and otherwise healthy. MAIN BODY: Preclinical models have provided us with possible mechanisms to explain the increased vulnerability of migraineurs’ brains towards ischemia and suggest a key role for enhanced cerebral excitability and increased incidence of microembolic events. Spreading depolarization (SD), a slowly propagating wave of neuronal depolarization, is the electrophysiologic event underlying migraine aura and a known headache trigger. Increased SD susceptibility has been demonstrated in migraine animal models, including transgenic mice carrying human mutations for the migraine-associated syndrome CADASIL and familial hemiplegic migraine (type 1 and 2). Upon experimentally induced SD, these mice develop aura-like neurological symptoms, akin to patients with the respective mutations. Migraine mutant mice also exhibit an increased frequency of ischemia-triggered SDs upon experimental stroke, associated with accelerated infarct growth and worse outcomes. The severe stroke phenotype can be explained by SD-related downstream events that exacerbate the metabolic mismatch, including pericyte contraction and neuroglial inflammation. Pharmacological suppression of the genetically enhanced SD susceptibility normalizes the stroke phenotype in familial hemiplegic migraine mutant mice. Recent epidemiologic and imaging studies suggest that these preclinical findings can be extrapolated to migraine patients. Migraine patients are at risk for particularly cardioembolic stroke. At the same time, studies suggest an increased incidence of coagulopathy, atrial fibrillation and patent foramen ovale among migraineurs, providing a possible path for microembolic induction of SD and, in rare instances, stroke in hyperexcitable brains. Indeed, recent imaging studies document an accelerated infarct progression with only little potentially salvageable brain tissue in acute stroke patients with a migraine history, suggesting an increased vulnerability towards cerebral ischemia. CONCLUSION: Preclinical models suggest a key role for enhanced SD susceptibility and microembolization to explain both the occurrence of migraine attacks and the increased stroke risk in migraineurs. Therapeutic targeting of SD and microembolic events, or potential causes thereof, will be promising for treatment of aura and may also prevent ischemic infarction in vulnerable brains. |
format | Online Article Text |
id | pubmed-6734247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer Milan |
record_format | MEDLINE/PubMed |
spelling | pubmed-67342472019-09-12 Aura and Stroke: relationship and what we have learnt from preclinical models Yemisci, Muge Eikermann-Haerter, Katharina J Headache Pain Review Article BACKGROUND: Population-based studies have highlighted a close relationship between migraine and stroke. Migraine, especially with aura, is a risk factor for both ischemic and hemorrhagic stroke. Interestingly, stroke risk is highest for migraineurs who are young and otherwise healthy. MAIN BODY: Preclinical models have provided us with possible mechanisms to explain the increased vulnerability of migraineurs’ brains towards ischemia and suggest a key role for enhanced cerebral excitability and increased incidence of microembolic events. Spreading depolarization (SD), a slowly propagating wave of neuronal depolarization, is the electrophysiologic event underlying migraine aura and a known headache trigger. Increased SD susceptibility has been demonstrated in migraine animal models, including transgenic mice carrying human mutations for the migraine-associated syndrome CADASIL and familial hemiplegic migraine (type 1 and 2). Upon experimentally induced SD, these mice develop aura-like neurological symptoms, akin to patients with the respective mutations. Migraine mutant mice also exhibit an increased frequency of ischemia-triggered SDs upon experimental stroke, associated with accelerated infarct growth and worse outcomes. The severe stroke phenotype can be explained by SD-related downstream events that exacerbate the metabolic mismatch, including pericyte contraction and neuroglial inflammation. Pharmacological suppression of the genetically enhanced SD susceptibility normalizes the stroke phenotype in familial hemiplegic migraine mutant mice. Recent epidemiologic and imaging studies suggest that these preclinical findings can be extrapolated to migraine patients. Migraine patients are at risk for particularly cardioembolic stroke. At the same time, studies suggest an increased incidence of coagulopathy, atrial fibrillation and patent foramen ovale among migraineurs, providing a possible path for microembolic induction of SD and, in rare instances, stroke in hyperexcitable brains. Indeed, recent imaging studies document an accelerated infarct progression with only little potentially salvageable brain tissue in acute stroke patients with a migraine history, suggesting an increased vulnerability towards cerebral ischemia. CONCLUSION: Preclinical models suggest a key role for enhanced SD susceptibility and microembolization to explain both the occurrence of migraine attacks and the increased stroke risk in migraineurs. Therapeutic targeting of SD and microembolic events, or potential causes thereof, will be promising for treatment of aura and may also prevent ischemic infarction in vulnerable brains. Springer Milan 2019-05-29 /pmc/articles/PMC6734247/ /pubmed/31142262 http://dx.doi.org/10.1186/s10194-019-1016-x Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Review Article Yemisci, Muge Eikermann-Haerter, Katharina Aura and Stroke: relationship and what we have learnt from preclinical models |
title | Aura and Stroke: relationship and what we have learnt from preclinical models |
title_full | Aura and Stroke: relationship and what we have learnt from preclinical models |
title_fullStr | Aura and Stroke: relationship and what we have learnt from preclinical models |
title_full_unstemmed | Aura and Stroke: relationship and what we have learnt from preclinical models |
title_short | Aura and Stroke: relationship and what we have learnt from preclinical models |
title_sort | aura and stroke: relationship and what we have learnt from preclinical models |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734247/ https://www.ncbi.nlm.nih.gov/pubmed/31142262 http://dx.doi.org/10.1186/s10194-019-1016-x |
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