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Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD
Spreading depolarization (SD) occurs in a plethora of clinical conditions including migraine aura, delayed ischemia after subarachnoid hemorrhage and malignant hemispheric stroke. It describes waves of near-breakdown of ion homeostasis, particularly Na(+) homeostasis in brain gray matter. SD induces...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903222/ https://www.ncbi.nlm.nih.gov/pubmed/36329390 http://dx.doi.org/10.1177/0271678X221135085 |
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author | Kang, Eun-Jeung Prager, Ofer Lublinsky, Svetlana Oliveira-Ferreira, Ana I Reiffurth, Clemens Major, Sebastian Müller, Dominik N Friedman, Alon Dreier, Jens P |
author_facet | Kang, Eun-Jeung Prager, Ofer Lublinsky, Svetlana Oliveira-Ferreira, Ana I Reiffurth, Clemens Major, Sebastian Müller, Dominik N Friedman, Alon Dreier, Jens P |
author_sort | Kang, Eun-Jeung |
collection | PubMed |
description | Spreading depolarization (SD) occurs in a plethora of clinical conditions including migraine aura, delayed ischemia after subarachnoid hemorrhage and malignant hemispheric stroke. It describes waves of near-breakdown of ion homeostasis, particularly Na(+) homeostasis in brain gray matter. SD induces tone alterations in resistance vessels, causing either hyperperfusion in healthy tissue; or hypoperfusion (inverse hemodynamic response = spreading ischemia) in tissue at risk. Observations from mice with genetic dysfunction of the ATP1A2-encoded α(2)-isoform of Na(+)/K(+)-ATPase (α(2)NaKA) suggest a mechanistic link between (1) SD, (2) vascular dysfunction, and (3) salt-sensitive hypertension via α(2)NaKA. Thus, α(2)NaKA-dysfunctional mice are more susceptible to SD and show a shift toward more inverse hemodynamic responses. α(2)NaKA-dysfunctional patients suffer from familial hemiplegic migraine type 2, a Mendelian model disease of SD. α(2)NaKA-dysfunctional mice are also a genetic model of salt-sensitive hypertension. To determine whether SD thresholds and hemodynamic responses are also altered in other genetic models of salt-sensitive hypertension, we examined these variables in stroke-prone spontaneously hypertensive rats (SHRsp). Compared with Wistar Kyoto control rats, we found in SHRsp that electrical SD threshold was significantly reduced, propagation speed was increased, and inverse hemodynamic responses were prolonged. These results may have relevance to both migraine with aura and stroke. |
format | Online Article Text |
id | pubmed-9903222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-99032222023-02-08 Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD Kang, Eun-Jeung Prager, Ofer Lublinsky, Svetlana Oliveira-Ferreira, Ana I Reiffurth, Clemens Major, Sebastian Müller, Dominik N Friedman, Alon Dreier, Jens P J Cereb Blood Flow Metab Original Articles Spreading depolarization (SD) occurs in a plethora of clinical conditions including migraine aura, delayed ischemia after subarachnoid hemorrhage and malignant hemispheric stroke. It describes waves of near-breakdown of ion homeostasis, particularly Na(+) homeostasis in brain gray matter. SD induces tone alterations in resistance vessels, causing either hyperperfusion in healthy tissue; or hypoperfusion (inverse hemodynamic response = spreading ischemia) in tissue at risk. Observations from mice with genetic dysfunction of the ATP1A2-encoded α(2)-isoform of Na(+)/K(+)-ATPase (α(2)NaKA) suggest a mechanistic link between (1) SD, (2) vascular dysfunction, and (3) salt-sensitive hypertension via α(2)NaKA. Thus, α(2)NaKA-dysfunctional mice are more susceptible to SD and show a shift toward more inverse hemodynamic responses. α(2)NaKA-dysfunctional patients suffer from familial hemiplegic migraine type 2, a Mendelian model disease of SD. α(2)NaKA-dysfunctional mice are also a genetic model of salt-sensitive hypertension. To determine whether SD thresholds and hemodynamic responses are also altered in other genetic models of salt-sensitive hypertension, we examined these variables in stroke-prone spontaneously hypertensive rats (SHRsp). Compared with Wistar Kyoto control rats, we found in SHRsp that electrical SD threshold was significantly reduced, propagation speed was increased, and inverse hemodynamic responses were prolonged. These results may have relevance to both migraine with aura and stroke. SAGE Publications 2022-11-03 2023-02 /pmc/articles/PMC9903222/ /pubmed/36329390 http://dx.doi.org/10.1177/0271678X221135085 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Articles Kang, Eun-Jeung Prager, Ofer Lublinsky, Svetlana Oliveira-Ferreira, Ana I Reiffurth, Clemens Major, Sebastian Müller, Dominik N Friedman, Alon Dreier, Jens P Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD |
title | Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD |
title_full | Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD |
title_fullStr | Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD |
title_full_unstemmed | Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD |
title_short | Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD |
title_sort | stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (sd) and altered hemodynamic responses to sd |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903222/ https://www.ncbi.nlm.nih.gov/pubmed/36329390 http://dx.doi.org/10.1177/0271678X221135085 |
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