Figure 5.

Loss of BBB integrity at 3 d is due primarily to increased transcytosis and not tight junctional complex disassembly. A, Representative toluidine blue-stained section of embedded tissue. Scale bar, 250 μm. Inset, Example of peri-infarct capillaries (arrowheads) suitable for electron microscopy. Scale bars: middle, 100 μm; right, 10 μm. B, Electron micrograph showing a capillary in the undamaged contralateral hemisphere of a nondiabetic mouse, 3 d after stroke. Inset, Intact tight junctions (arrowhead) and generally thin endothelium. Scale bar, 2 μm. C, Peri-infarct capillary 3 d after stroke. Insets, Tight junctions of the capillary are intact (arrowheads). Scale bar, 2 μm. D, Peri-infarct capillary 3 d after stroke. Inset, Thickened endothelium and large increase in caveolae-like vesicles. Scale bar, 2 μm. E, Bright-field image of coronal section from HRP-injected mouse, reacted with 3,3′ diaminobenzidine, generating electron dense brown reaction product around the infarct. Scale bar, 1.0 mm. F, Capillary in the contralateral control hemisphere showing little HRP staining 3 d after stroke. G, H, Representative electron micrographs showing increased HRP reaction product in the endothelium of capillaries in the peri-infarct cortex of nondiabetic and diabetic mice. Scale bar: F–H, 0.5 μm. I, Diabetic peri-infarct capillary 3 d after stroke and higher-magnification image of boxed region showing 5 nm gold particles (arrows) present in vesicles within the endothelium, basement membrane (BM), and adjacent glial cells. Scale bar, 1 μm. Scale bar: inset, 100 nm.