Blood-brain barrier breakdown after embolic stroke in rats occurs without ultrastructural evidence for disrupting tight junctions.

摘要: The term blood-brain barrier (BBB) relates to the ability of cerebral vessels hold back hydrophilic and large molecules from entering brain, thereby crucially contributing brain homeostasis. In fact, experimental opening endothelial tight junctions causes a breakdown BBB evidenced as for instance by albumin leakage. This similar observations led conclusion that is predominantly mediated damage junction complexes, but evidentiary ultrastructural data are rare. Since functional deficits contribute an increased risk hemorrhagic transformation edema after stroke, which both critically impact on clinical outcome, we studied mechanism using embolic model focal ischemia in Wistar rats closely mimic essential human pathophysiology. Ischemia-induced was detected intravenous injection FITC-albumin areas extravasation were subsequently fluorescence electron microscopy. Against our expectation, 25 hours induction morphology complexes (identified ultrastructurally antibodies against transcellular proteins occludin claudin-5) appeared be regularly maintained regions where massively leaked into neuropil. Furthermore, signals along pan-laminin-labeled affected hemisphere equaled non-affected contralateral side (ratio: 0.966 vs. 0.963; P = 0.500). Additional analyses at 5 h clearly indicated around with intact junctions, while endothelium exhibited enhanced transendothelial vesicle trafficking signs degeneration. Thus, leakage cannot correlated staining patterns common alone. Understanding mechanisms causing alterations likely provide novel protective targets stroke.