CASM in relation to Blood brain barrier integrity in case of ischemic/reperfusion injury.

Ischemic stroke-induced blood-brain barrier (BBB) disruption plays a critical role in the progression of neuroinflammation and exacerbates neuronal injury. The LANDO pathway involved in endocytosis has been implicated in regulating receptor recycling and immune cell responses. Using LANDO-deficient transgenic mice, we investigated the role of LANDO in ischemia-induced BBB dysfunction. Our results show that LANDO deficiency leads to increased BBB permeability and more severe cerebral edema, as evidenced by Evans blue extravasation and plasma IgG infiltration. This heightened permeability correlates with an increase in infarct size, neurological deficits, and reduced survival. Notably, LANDO deficiency impairs junctional protein redistribution in cerebral microvessels occludin and VE-cadherin, leading to compromised endothelial barrier function. In vitro, LANDO-deficient brain microvascular endothelial cells exhibit greater endothelial permeability, as measured by dextran-FITC and transendothelial resistance assays. Furthermore, LANDO-deficient mice show enhanced neutrophil infiltration as demonstrated by increased Lys6G and CitH3 levels and persistent microglial activation post-tFCI.