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Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage

Subarachnoid haemorrhage (SAH) is a type of hemorrhagic stroke that is associated with high morbidity and mortality. New effective treatments are needed to improve outcomes. The pathophysiology of SAH is complex and includes early brain injury and delayed cerebral ischemia, both of which are charact...

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Autores principales: Tso, Michael K., Turgeon, Paul, Bosche, Bert, Lee, Charles K., Nie, Tian, D’Abbondanza, Josephine, Ai, Jinglu, Marsden, Philip A., Macdonald, R. Loch
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035152/
https://www.ncbi.nlm.nih.gov/pubmed/33837224
http://dx.doi.org/10.1038/s41598-021-87301-z
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author Tso, Michael K.
Turgeon, Paul
Bosche, Bert
Lee, Charles K.
Nie, Tian
D’Abbondanza, Josephine
Ai, Jinglu
Marsden, Philip A.
Macdonald, R. Loch
author_facet Tso, Michael K.
Turgeon, Paul
Bosche, Bert
Lee, Charles K.
Nie, Tian
D’Abbondanza, Josephine
Ai, Jinglu
Marsden, Philip A.
Macdonald, R. Loch
author_sort Tso, Michael K.
collection PubMed
description Subarachnoid haemorrhage (SAH) is a type of hemorrhagic stroke that is associated with high morbidity and mortality. New effective treatments are needed to improve outcomes. The pathophysiology of SAH is complex and includes early brain injury and delayed cerebral ischemia, both of which are characterized by blood–brain barrier (BBB) impairment. We isolated brain endothelial cells (BECs) from mice subjected to SAH by injection of blood into the prechiasmatic cistern. We used gene expression profiling to identify 707 unique genes (2.8% of transcripts, 403 upregulated, 304 downregulated, 24,865 interrogated probe sets) that were significantly differentially expressed in mouse BECs after SAH. The pathway involving prostaglandin synthesis and regulation was significantly upregulated after SAH, including increased expression of the Ptgs2 gene and its corresponding COX-2 protein. Celecoxib, a selective COX-2 inhibitor, limited upregulation of Ptgs2 in BECs. In this study, we have defined the gene expression profiling of BECs after experimental SAH and provide further insight into BBB pathophysiology, which may be relevant to other neurological diseases such as traumatic brain injury, brain tumours, ischaemic stroke, multiple sclerosis, and neurodegenerative disorders.
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spelling pubmed-80351522021-04-13 Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage Tso, Michael K. Turgeon, Paul Bosche, Bert Lee, Charles K. Nie, Tian D’Abbondanza, Josephine Ai, Jinglu Marsden, Philip A. Macdonald, R. Loch Sci Rep Article Subarachnoid haemorrhage (SAH) is a type of hemorrhagic stroke that is associated with high morbidity and mortality. New effective treatments are needed to improve outcomes. The pathophysiology of SAH is complex and includes early brain injury and delayed cerebral ischemia, both of which are characterized by blood–brain barrier (BBB) impairment. We isolated brain endothelial cells (BECs) from mice subjected to SAH by injection of blood into the prechiasmatic cistern. We used gene expression profiling to identify 707 unique genes (2.8% of transcripts, 403 upregulated, 304 downregulated, 24,865 interrogated probe sets) that were significantly differentially expressed in mouse BECs after SAH. The pathway involving prostaglandin synthesis and regulation was significantly upregulated after SAH, including increased expression of the Ptgs2 gene and its corresponding COX-2 protein. Celecoxib, a selective COX-2 inhibitor, limited upregulation of Ptgs2 in BECs. In this study, we have defined the gene expression profiling of BECs after experimental SAH and provide further insight into BBB pathophysiology, which may be relevant to other neurological diseases such as traumatic brain injury, brain tumours, ischaemic stroke, multiple sclerosis, and neurodegenerative disorders. Nature Publishing Group UK 2021-04-09 /pmc/articles/PMC8035152/ /pubmed/33837224 http://dx.doi.org/10.1038/s41598-021-87301-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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 Article
Tso, Michael K.
Turgeon, Paul
Bosche, Bert
Lee, Charles K.
Nie, Tian
D’Abbondanza, Josephine
Ai, Jinglu
Marsden, Philip A.
Macdonald, R. Loch
Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage
title Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage
title_full Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage
title_fullStr Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage
title_full_unstemmed Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage
title_short Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage
title_sort gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035152/
https://www.ncbi.nlm.nih.gov/pubmed/33837224
http://dx.doi.org/10.1038/s41598-021-87301-z
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