β1 integrin is essential for blood–brain barrier integrity under stable and vascular remodelling conditions; effects differ with age

作者：Sebok K. Halder, Violaine Delorme-Walker, Richard Milner · 发表于：Fluids and Barriers of the CNS · 年份：2023 · DOI：10.1186/s12987-023-00453-0 · 被引用次数：19 · 研究领域：Barrier Structure and Function Studies、Cell Adhesion Molecules Research、Alzheimer's disease research and treatments

BACKGROUND: Maintaining a tight blood-brain barrier (BBB) is an important prerequisite for the preservation of neurological health, though current evidence suggests it declines with age. While extracellular matrix-integrin interactions play critical roles in regulating the balance between vascular stability and remodeling, it remains to be established whether manipulation of integrin function weakens or strengthens vascular integrity. Indeed, recent reports have generated conflicting outcomes in this regard. METHODS: ) conditions, when a vigorous vascular remodeling response is ongoing. Brain tissue was examined by immunofluorescence (IF) for markers of vascular remodeling and BBB disruption, and microglial activation and proliferation. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's multiple comparison post-hoc test. RESULTS: In both young and aged mice, β1 integrin block greatly amplified hypoxia-induced vascular disruption, though it was much less under normoxic conditions. Interestingly, under both normoxic and hypoxic conditions, β1 integrin antibody-induced BBB disruption was greater in young mice. Enhanced BBB breakdown was associated with increased levels of the leaky BBB marker MECA-32 and with greater loss of endothelial tight junction proteins and the adherens protein VE-cadherin. Surprisingly, β1 integrin blockade did not reduce hypoxia-induced endothelial proliferation, nor did it prevent the hypoxia-associated increase in vascul...