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

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

  • Biochem Biophys Res Commun. 2024 Sep 10:724:150216. doi: 10.1016/j.bbrc.2024.150216.
Zhijiang Gu 1,  Shaoxun Li 1,  Jiyu Liu 2,  Xiaotian Zhang 1,  Cong Pang 1,  Lianshu Ding 3,  Changchun Cao 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, 223300, China.
  • 2 Huaian Clinical College of Xuzhou Medical University, Huaian, 223300, China.
  • 3 Department of Neurosurgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, 223300, China. Electronic address: dlshu@163.com.
  • 4 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.
PMID: 38851140 DOI: 10.1016/j.bbrc.2024.150216
Abstract

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 Dapk1fl/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 A2 (cPLA2) in OGD-stimulated CECs. Our results thus suggest that inhibition of endothelial DAPK1 specifically prevents BBB damage after stroke.

Keywords

Interaction; Kinase; Permeability; Phosphorylation; Stroke.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15513
    98.26%, DAPK Inhibitor