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The role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model

Spreading depolarization (SD) and seizures are pathophysiological events associated with cerebral ischemia. Here, we investigated their role for injury progression in the cerebral cortex. Cerebral ischemia was induced in anesthetized male Wistar rats using the photothrombosis (PT) stroke model. SD a...

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Autores principales: Schoknecht, Karl, Kikhia, Majed, Lemale, Coline L, Liotta, Agustin, Lublinsky, Svetlana, Mueller, Susanne, Boehm-Sturm, Philipp, Friedman, Alon, Dreier, Jens P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812510/
https://www.ncbi.nlm.nih.gov/pubmed/32241203
http://dx.doi.org/10.1177/0271678X20915801
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author Schoknecht, Karl
Kikhia, Majed
Lemale, Coline L
Liotta, Agustin
Lublinsky, Svetlana
Mueller, Susanne
Boehm-Sturm, Philipp
Friedman, Alon
Dreier, Jens P
author_facet Schoknecht, Karl
Kikhia, Majed
Lemale, Coline L
Liotta, Agustin
Lublinsky, Svetlana
Mueller, Susanne
Boehm-Sturm, Philipp
Friedman, Alon
Dreier, Jens P
author_sort Schoknecht, Karl
collection PubMed
description Spreading depolarization (SD) and seizures are pathophysiological events associated with cerebral ischemia. Here, we investigated their role for injury progression in the cerebral cortex. Cerebral ischemia was induced in anesthetized male Wistar rats using the photothrombosis (PT) stroke model. SD and spontaneous neuronal activity were recorded in the presence of either urethane or ketamine/xylazine anesthesia. Blood–brain barrier (BBB) permeability, cerebral perfusion, and cellular damage were assessed through a cranial window and repeated intravenous injection of fluorescein sodium salt and propidium iodide until 4 h after PT. Neuronal injury and early lesion volume were quantified by stereological cell counting and manual and automated assessment of ex vivo T2-weighted magnetic resonance imaging. Onset SDs originated at the thrombotic core and invaded neighboring cortex, whereas delayed SDs often showed opposite propagation patterns. Seizure induction by 4-aminopyridine caused no increase in lesion volume or neuronal injury in urethane-anesthetized animals. Ketamine/xylazine anesthesia was associated with a lower number of onset SDs, reduced lesion volume, and neuronal injury despite a longer duration of seizures. BBB permeability increase inversely correlated with the number of SDs at 3 and 4 h after PT. Our results provide further evidence that ketamine may counteract the early progression of ischemic injury.
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spelling pubmed-78125102021-01-26 The role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model Schoknecht, Karl Kikhia, Majed Lemale, Coline L Liotta, Agustin Lublinsky, Svetlana Mueller, Susanne Boehm-Sturm, Philipp Friedman, Alon Dreier, Jens P J Cereb Blood Flow Metab Original Articles Spreading depolarization (SD) and seizures are pathophysiological events associated with cerebral ischemia. Here, we investigated their role for injury progression in the cerebral cortex. Cerebral ischemia was induced in anesthetized male Wistar rats using the photothrombosis (PT) stroke model. SD and spontaneous neuronal activity were recorded in the presence of either urethane or ketamine/xylazine anesthesia. Blood–brain barrier (BBB) permeability, cerebral perfusion, and cellular damage were assessed through a cranial window and repeated intravenous injection of fluorescein sodium salt and propidium iodide until 4 h after PT. Neuronal injury and early lesion volume were quantified by stereological cell counting and manual and automated assessment of ex vivo T2-weighted magnetic resonance imaging. Onset SDs originated at the thrombotic core and invaded neighboring cortex, whereas delayed SDs often showed opposite propagation patterns. Seizure induction by 4-aminopyridine caused no increase in lesion volume or neuronal injury in urethane-anesthetized animals. Ketamine/xylazine anesthesia was associated with a lower number of onset SDs, reduced lesion volume, and neuronal injury despite a longer duration of seizures. BBB permeability increase inversely correlated with the number of SDs at 3 and 4 h after PT. Our results provide further evidence that ketamine may counteract the early progression of ischemic injury. SAGE Publications 2020-04-02 2021-02 /pmc/articles/PMC7812510/ /pubmed/32241203 http://dx.doi.org/10.1177/0271678X20915801 Text en © The Author(s) 2020 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
Schoknecht, Karl
Kikhia, Majed
Lemale, Coline L
Liotta, Agustin
Lublinsky, Svetlana
Mueller, Susanne
Boehm-Sturm, Philipp
Friedman, Alon
Dreier, Jens P
The role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model
title The role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model
title_full The role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model
title_fullStr The role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model
title_full_unstemmed The role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model
title_short The role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model
title_sort role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812510/
https://www.ncbi.nlm.nih.gov/pubmed/32241203
http://dx.doi.org/10.1177/0271678X20915801
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