Critical role of Slc22a8 in maintaining blood-brain barrier integrity after experimental cerebral ischemia-reperfusion.
J Cereb Blood Flow Metab
; : 271678X241264401, 2024 Jul 28.
Article
em En
| MEDLINE
| ID: mdl-39068534
ABSTRACT
Blood-brain barrier (BBB) damage significantly affects the prognosis of ischemic stroke patients. This project employed multi-omics analysis to identify key factors regulating BBB disruption during cerebral ischemia-reperfusion. An integrated analysis of three transcriptome sequencing datasets from mouse middle cerebral artery occlusion/reperfusion (MCAO/R) models identified eight downregulated genes in endothelial cells. Additionally, transcriptome analysis of BBB (cortex) and non-BBB (lung) endothelium of E13.5 mice revealed 2,102 upregulated genes potentially associated with BBB integrity. The eight downregulated genes were intersected with the 2,102 BBB-related genes and mapped using single-cell RNA sequencing data, revealing that solute carrier family 22 member 8 (Slc22a8) is specifically expressed in endothelial cells and pericytes and significantly decreases after MCAO/R. This finding was validated in the mouse MCAO/R model at both protein and mRNA levels in this study. External overexpression of Slc22a8 using a lentivirus carrying Tie2 improved Slc22a8 and tight junction protein levels and reduced BBB leakage after MCAO/R, accompanied by Wnt/ß-catenin signaling activation. In conclusion, this study suggested that MCAO/R-induced downregulation of Slc22a8 expression may be a crucial mechanism underlying BBB disruption. Interventions that promote Slc22a8 expression or enhance its function hold promise for improving the prognosis of patients with cerebral ischemia.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Cereb Blood Flow Metab
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China