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Spreading depolarizations in the rat endothelin-1 model of focal cerebellar ischemia

Focal brain ischemia is best studied in neocortex and striatum. Both show highly vulnerable neurons and high susceptibility to spreading depolarization (SD). Therefore, it has been hypothesized that these two variables generally correlate. However, this hypothesis is contradicted by findings in cere...

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Autores principales: Oliveira-Ferreira, Ana I, Major, Sebastian, Przesdzing, Ingo, Kang, Eun-Jeung, Dreier, Jens P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232780/
https://www.ncbi.nlm.nih.gov/pubmed/31280632
http://dx.doi.org/10.1177/0271678X19861604
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author Oliveira-Ferreira, Ana I
Major, Sebastian
Przesdzing, Ingo
Kang, Eun-Jeung
Dreier, Jens P
author_facet Oliveira-Ferreira, Ana I
Major, Sebastian
Przesdzing, Ingo
Kang, Eun-Jeung
Dreier, Jens P
author_sort Oliveira-Ferreira, Ana I
collection PubMed
description Focal brain ischemia is best studied in neocortex and striatum. Both show highly vulnerable neurons and high susceptibility to spreading depolarization (SD). Therefore, it has been hypothesized that these two variables generally correlate. However, this hypothesis is contradicted by findings in cerebellar cortex, which contains highly vulnerable neurons to ischemia, the Purkinje cells, but is said to be less susceptible to SD. Here, we found in the rat cerebellar cortex that elevated K(+) induced a long-lasting depolarizing event superimposed with SDs. Cerebellar SDs resembled those in neocortex, but negative direct current (DC) shifts and regional blood flow responses were usually smaller. The K(+) threshold for SD was higher in cerebellum than in previous studies in neocortex. We then topically applied endothelin-1 (ET-1) to the cerebellum, which is assumed to cause SD via vasoconstriction-induced focal ischemia. Although the blood flow decrease was similar to that in previous studies in neocortex, the ET-1 threshold for SD was higher. Quantitative cell counting found that the proportion of necrotic Purkinje cells was significantly higher in ET-1-treated rats than sham controls even if ET-1 had not caused SDs. Our results suggest that ischemic death of Purkinje cells does not require the occurrence of SD.
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spelling pubmed-72327802020-06-15 Spreading depolarizations in the rat endothelin-1 model of focal cerebellar ischemia Oliveira-Ferreira, Ana I Major, Sebastian Przesdzing, Ingo Kang, Eun-Jeung Dreier, Jens P J Cereb Blood Flow Metab Original Articles Focal brain ischemia is best studied in neocortex and striatum. Both show highly vulnerable neurons and high susceptibility to spreading depolarization (SD). Therefore, it has been hypothesized that these two variables generally correlate. However, this hypothesis is contradicted by findings in cerebellar cortex, which contains highly vulnerable neurons to ischemia, the Purkinje cells, but is said to be less susceptible to SD. Here, we found in the rat cerebellar cortex that elevated K(+) induced a long-lasting depolarizing event superimposed with SDs. Cerebellar SDs resembled those in neocortex, but negative direct current (DC) shifts and regional blood flow responses were usually smaller. The K(+) threshold for SD was higher in cerebellum than in previous studies in neocortex. We then topically applied endothelin-1 (ET-1) to the cerebellum, which is assumed to cause SD via vasoconstriction-induced focal ischemia. Although the blood flow decrease was similar to that in previous studies in neocortex, the ET-1 threshold for SD was higher. Quantitative cell counting found that the proportion of necrotic Purkinje cells was significantly higher in ET-1-treated rats than sham controls even if ET-1 had not caused SDs. Our results suggest that ischemic death of Purkinje cells does not require the occurrence of SD. SAGE Publications 2019-07-07 2020-06 /pmc/articles/PMC7232780/ /pubmed/31280632 http://dx.doi.org/10.1177/0271678X19861604 Text en © The Author(s) 2019 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits non-commercial 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
Oliveira-Ferreira, Ana I
Major, Sebastian
Przesdzing, Ingo
Kang, Eun-Jeung
Dreier, Jens P
Spreading depolarizations in the rat endothelin-1 model of focal cerebellar ischemia
title Spreading depolarizations in the rat endothelin-1 model of focal cerebellar ischemia
title_full Spreading depolarizations in the rat endothelin-1 model of focal cerebellar ischemia
title_fullStr Spreading depolarizations in the rat endothelin-1 model of focal cerebellar ischemia
title_full_unstemmed Spreading depolarizations in the rat endothelin-1 model of focal cerebellar ischemia
title_short Spreading depolarizations in the rat endothelin-1 model of focal cerebellar ischemia
title_sort spreading depolarizations in the rat endothelin-1 model of focal cerebellar ischemia
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232780/
https://www.ncbi.nlm.nih.gov/pubmed/31280632
http://dx.doi.org/10.1177/0271678X19861604
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