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Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism

The breakdown of the blood–brain barrier (BBB) is a critical event in the development of secondary brain injury after stroke. Among the cellular hallmarks in the acute phase after stroke are a downregulation of tight-junction molecules and the loss of microvascular pericyte coverage and endothelial...

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Autores principales: Ghori, Adnan, Prinz, Vincent, Nieminen-Kehlä, Melina, Bayerl, Simon. H., Kremenetskaia, Irina, Riecke, Jana, Krechel, Hanna, Broggini, Thomas, Scherschinski, Lea, Licht, Tamar, Keshet, Eli, Vajkoczy, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9391249/
https://www.ncbi.nlm.nih.gov/pubmed/35175562
http://dx.doi.org/10.1007/s12975-022-00991-z
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author Ghori, Adnan
Prinz, Vincent
Nieminen-Kehlä, Melina
Bayerl, Simon. H.
Kremenetskaia, Irina
Riecke, Jana
Krechel, Hanna
Broggini, Thomas
Scherschinski, Lea
Licht, Tamar
Keshet, Eli
Vajkoczy, Peter
author_facet Ghori, Adnan
Prinz, Vincent
Nieminen-Kehlä, Melina
Bayerl, Simon. H.
Kremenetskaia, Irina
Riecke, Jana
Krechel, Hanna
Broggini, Thomas
Scherschinski, Lea
Licht, Tamar
Keshet, Eli
Vajkoczy, Peter
author_sort Ghori, Adnan
collection PubMed
description The breakdown of the blood–brain barrier (BBB) is a critical event in the development of secondary brain injury after stroke. Among the cellular hallmarks in the acute phase after stroke are a downregulation of tight-junction molecules and the loss of microvascular pericyte coverage and endothelial sealing. Thus, a rapid repair of blood vessel integrity and re-stabilization of the BBB is considered an important strategy to reduce secondary brain damage. However, the mechanisms underlying BBB disruption remain poorly understood. Especially, the role of VEGF in this context remains inconclusive. With the conditional and reversible VEGF expression systems, we studied the time windows of deleterious and beneficial VEGF actions on blood vessel integrity in mice. Using genetic systems for gain of function and loss of function experiments, we activated and inhibited VEGF signaling prior and simultaneously to ischemic stroke onset. In both scenarios, VEGF seems to play a vital role in containing the stroke-induced damage after cerebral ischemia. We report that the transgenic overexpression of VEGF (GOF) prior to the stroke stabilizes the vasculature and prevents blood–brain barrier disruption in young and aged animals after stroke. Whereas inhibition of signals for endogenous VEGF (LOF) prior to stroke results in bigger infarction with massive brain swelling and enhanced BBB permeability, furthermore, activating or blocking VEGF signaling after ischemic stroke onset had comparable effects on BBB repair and cerebral edema. VEGF can function as an anti-permeability factor, and a VEGF-based therapy in the context of stroke prevention and recovery has an enormous potential. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12975-022-00991-z.
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spelling pubmed-93912492022-08-21 Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism Ghori, Adnan Prinz, Vincent Nieminen-Kehlä, Melina Bayerl, Simon. H. Kremenetskaia, Irina Riecke, Jana Krechel, Hanna Broggini, Thomas Scherschinski, Lea Licht, Tamar Keshet, Eli Vajkoczy, Peter Transl Stroke Res Original Article The breakdown of the blood–brain barrier (BBB) is a critical event in the development of secondary brain injury after stroke. Among the cellular hallmarks in the acute phase after stroke are a downregulation of tight-junction molecules and the loss of microvascular pericyte coverage and endothelial sealing. Thus, a rapid repair of blood vessel integrity and re-stabilization of the BBB is considered an important strategy to reduce secondary brain damage. However, the mechanisms underlying BBB disruption remain poorly understood. Especially, the role of VEGF in this context remains inconclusive. With the conditional and reversible VEGF expression systems, we studied the time windows of deleterious and beneficial VEGF actions on blood vessel integrity in mice. Using genetic systems for gain of function and loss of function experiments, we activated and inhibited VEGF signaling prior and simultaneously to ischemic stroke onset. In both scenarios, VEGF seems to play a vital role in containing the stroke-induced damage after cerebral ischemia. We report that the transgenic overexpression of VEGF (GOF) prior to the stroke stabilizes the vasculature and prevents blood–brain barrier disruption in young and aged animals after stroke. Whereas inhibition of signals for endogenous VEGF (LOF) prior to stroke results in bigger infarction with massive brain swelling and enhanced BBB permeability, furthermore, activating or blocking VEGF signaling after ischemic stroke onset had comparable effects on BBB repair and cerebral edema. VEGF can function as an anti-permeability factor, and a VEGF-based therapy in the context of stroke prevention and recovery has an enormous potential. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12975-022-00991-z. Springer US 2022-02-17 2022 /pmc/articles/PMC9391249/ /pubmed/35175562 http://dx.doi.org/10.1007/s12975-022-00991-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Ghori, Adnan
Prinz, Vincent
Nieminen-Kehlä, Melina
Bayerl, Simon. H.
Kremenetskaia, Irina
Riecke, Jana
Krechel, Hanna
Broggini, Thomas
Scherschinski, Lea
Licht, Tamar
Keshet, Eli
Vajkoczy, Peter
Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism
title Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism
title_full Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism
title_fullStr Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism
title_full_unstemmed Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism
title_short Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism
title_sort vascular endothelial growth factor augments the tolerance towards cerebral stroke by enhancing neurovascular repair mechanism
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9391249/
https://www.ncbi.nlm.nih.gov/pubmed/35175562
http://dx.doi.org/10.1007/s12975-022-00991-z
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