BCL-3 Promotes Intracerebral Hemorrhage Progression by Increasing Blood-Brain Barrier Permeability, Inflammation, and Cell Apoptosis via Endoplasmic Reticulum Stress.

BACKGROUND: Intracerebral hemorrhage (ICH) is among the common types of stroke with high mortality and morbidity. Molecular biomarker selection is crucial for ICH diagnosis and treatment. However, the identification of ICH-related biomarkers remains inadequate. MATERIALS AND METHODS: In vivo and in vitro ICH models were generated and transfected with silenced B-cell lymphoma-3 (BCL-3 and siRNA BCL-3), overexpressed BCL-3, and endoplasmic reticulum stress (ERS) agonist (2-CLHA). Hematoxylin-eosin staining and transmission electron microscopy were used to observe the transfected cells. RNA sequencing was performed in vivo on the sham and ICH groups. The blood-brain barrier (BBB) permeability was evaluated by determining Evans blue dye extravasation, transendothelial electrical resistance, and paracellular permeability. Moreover, tight junction-, cell apoptosis-, and endoplasmic reticulum stress- (ERS-) related proteins were evaluated through real-time quantitative PCR, western blotting, immunohistochemistry, and TUNEL staining. The levels of inflammatory cytokines were measured through the enzyme-linked immunosorbent assay. RESULTS: RNA-seq revealed that BCL-3 acts as a key player. BCL-3 promotes ICH progression by increasing BBB permeability, ERS, inflammation, and cell apoptosis. Silencing of BCL-3 slows ICH progression by reducing BBB permeability and inflammation and terminating cell apoptosis and ERS in vitro and in vivo. CONCLUSION: Our study identified ICH biomarkers and elucidated the role of BCL-3 in ICH for the first time.