Neuron

Brain endothelial cells form a paracellular and transcellular barrier to many blood-borne solutes via tight junctions (TJs) and scarce endocytotic vesicles. The blood-brain barrier (BBB) plays a pivotal role in the healthy and diseased CNS. BBB damage after ischemic stroke contributes to increased mortality, yet the contributions of paracellular and transcellular mechanisms to this process in vivo are unknown. We have created a transgenic mouse strain whose endothelial TJs are labeled with eGFP and have imaged dynamic TJ changes and fluorescent tracer leakage across the BBB in vivo, using two-photon microscopy in the t-MCAO stroke model. Although barrier function is impaired as early as 6 hr after stroke, TJs display profound structural defects only after 2 days. Conversely, the number of endothelial caveolae and transcytosis rate increase as early as 6 hr after stroke. Therefore, stepwise impairment of transcellular followed by paracellular barrier mechanisms accounts for the BBB deficits in stroke.1DP2NS083038/DP/NCCDPHP CDC HHS/United States1P01NS37520-08/NS/NINDS NIH HHS/United States1R01 HL116995-01/HL/NHLBI NIH HHS/United States2P30CA014195/CA/NCI NIH HHS/United StatesDP2 NS083038/NS/NINDS NIH HHS/United StatesR01 HL116995/HL/NHLBI NIH HHS/United States2015-05-07T00:00:00Z24746419PMC401616