Protection of blood-brain barrier by endothelial DAPK1 deletion after stroke.

Autor: Gu Z; Department of Neurosurgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, 223300, China., Li S; Department of Neurosurgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, 223300, China., Liu J; Huaian Clinical College of Xuzhou Medical University, Huaian, 223300, China., Zhang X; Department of Neurosurgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, 223300, China., Pang C; Department of Neurosurgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, 223300, China., Ding L; Department of Neurosurgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, 223300, China. Electronic address: dlshu@163.com., Cao C; Department of Pharmacy, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, 223300, China; Huaian Clinical College of Xuzhou Medical University, Huaian, 223300, China. Electronic address: caochangchun1986@sina.com.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Sep 10; Vol. 724, pp. 150216. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1016/j.bbrc.2024.150216
Abstrakt: Death-associated protein kinase (DAPK) 1 is a critical mediator for neuronal cell death in cerebral ischemia, but its role in blood-brain barrier (BBB) disruption is incompletely understood. Here, we found that endothelial-specific deletion of Dapk1 using Tie2 Cre protected the brain of Dapk1 fl/fl mice against middle cerebral artery occlusion (MCAO), characterized by mitigated Evans blue dye (EBD) extravasation, reduced infarct size and improved behavior. In vitro experiments also indicated that DAPK1 deletion inhibited oxygen-glucose deprivation (OGD)-induced tight junction alteration between cerebral endothelial cells (CECs). Mechanistically, we revealed that DAPK1-DAPK3 interaction activated cytosolic phospholipase A 2 (cPLA 2 ) in OGD-stimulated CECs. Our results thus suggest that inhibition of endothelial DAPK1 specifically prevents BBB damage after stroke.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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