Podocalyxin is required for maintaining blood–brain barrier function during acute inflammation

Significance This article demonstrates a role for podocalyxin in blood–brain barrier (BBB) function. Podocalyxin expression on endothelial cells promotes the formation of adhesion interactions and barrier formation. Furthermore, it describes a neuroelectric phenotype elicited by a selective protease-activated receptor-1 (PAR-1) agonist. PAR-1 activation by serum proteases (e.g., thrombin) leaking into the central nervous system during inflammation has the potential to impact the course of brain injury and recovery. However, the role of PAR-1 in the pathophysiology of neuroinflammation is poorly understood. In summary, this study offers unique insight into the impact of PAR-1 activation in neuroinflammation and implicates podocalyxin as a therapeutic target for the manipulation of BBB permeability and the treatment of neurodegenerative disease.