Peptide Science, Journal Year: 2025, Volume and Issue: 117(3)
Published: April 29, 2025
ABSTRACT The augmentation of blood–brain barrier (BBB) permeability is a key pathological characteristic sepsis‐associated encephalopathy (SAE). Pituitary adenylate cyclase‐activating polypeptide (PACAP), well‐known neuropeptide with potent anti‐inflammatory properties, has not yet been investigated for its potential beneficial effects in SAE. In this study, we aimed to explore aspect. First, the administration PACAP inhibited expression pro‐inflammatory cytokines interleukin‐1β (IL‐1β) and interleukin‐8 (IL‐8) mitigated brain vascular injury by reducing levels intercellular adhesion molecule‐1 (ICAM‐1) cell (VCAM‐1) brains septic mice. Importantly, preserved BBB integrity against lipopolysaccharide (LPS)‐induced disruption mice increasing both mRNA protein Claudin‐1. an vitro culture found that alleviated exacerbation endothelial increased transendothelial electrical resistance (TEER) LPS‐induced bEnd.3 cells, accompanied upregulation Consistently, protected reduction Wnt3a β‐catenin response LPS treatment cells. Notably, knockdown abolished restoring TEER levels, suggesting protective actions are mediated through Wnt3a/β‐catenin signaling pathway. Collectively, these findings demonstrate exerts on SAE modulating Wnt3a/β‐catenin/Claudin‐1
Language: Английский