Effect of tPA on cerebral ischemia-induced shedding of LRP's ectodomain. (A) Number of LRP-positive vascular structures in wild-type (WT) and tPA^−/− mice in the 3 AOIs 24 hours after MCAO. A subset of tPA^−/− mice was intracerebrally injected with murine tPA immediately after MCAO (tPA^−/− plus tPA). Error bars describe standard error of the mean; n = 6; *P < .005 relative to WT and tPA^−/− plus tPA. (B) Electron microscopy analysis of LRP in the NVU in the area of developing cerebral edema 24 hours after MCAO in tPA^−/− mice intracerebrally injected with either PBS (i,iii) or recombinant tPA (ii,iv) immediately after MCAO. Brains were stained with the R2629 anti-LRP antibody. Arrows in panel Bii depict the presence of LRP around the blood vessel. Asterisks in panel Bii, iii, and iv denote areas of perivascular edema. A indicates astrocyte; bv, blood vessel; ec, endothelial cell. Magnification, ×5000 (i-ii) and ×30 000 (iii-iv). Images were visualized using a Hitachi H-7500 electron microscope.