Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage

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作者
Michael K. Tso
Paul Turgeon
Bert Bosche
Charles K. Lee
Tian Nie
Josephine D’Abbondanza
Jinglu Ai
Philip A. Marsden
R. Loch Macdonald
机构
[1] University of Calgary,Division of Neurosurgery
[2] University of Toronto,Division of Neurosurgery, St. Michael’s Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael’s Hospital
[3] University of Toronto,Division of Nephrology
[4] MediClin Clinic Reichshof,Department of Neurocritical Care, Neurological and Neurosurgical First Stage Rehabilitation and Weaning
[5] University of Cologne,Institute of Neurophysiology
[6] University of Duisburg-Essen,Department of Neurology
[7] UCSF Fresno Campus,Department of Neurological Surgery
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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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