PS prevents postischemic BBB leakage in vivo via Tyro3 and S1P₁. (A) Immunoblotting of Tyro3, Axl, and Mer in mouse brain microvessels. (B) Two-photon in vivo imaging of fluorescein-conjugated dextran (F-dextran; MW = 70 000 kDa) leakage from cortical cerebral microvessels (layer II) in Tyro3^+/+ wild-type mice (left), Tyro3^−/− mice (middle), and Tyro3^+/+ mice pretreated with W146 (right) after 1-hour transient middle cerebral artery occlusion (MCAO) and 8-hour reperfusion. Murine PS (0.2 mg/kg) or saline was administered via the femoral vein 10 minutes after the MCAO. W146 was administered intraperitoneally 10 minutes before the MCAO. Bar (left and middle panels) represents 50 μm. Bar (right panels) represents 25 μm. (C-D) Quantification of F-dextran extravascular signal intensity (leakage) in brain parenchyma after 1-hour MCAO and 8-hour reperfusion in Tyro3^+/+, Tyro3^−/−, Axl^−/−, and Mer^−/− mice treated with vehicle or PS (C) and Tyro3^+/+ mice pretreated with W146 and treated with vehicle or PS (D). Sham-operated controls (mice that were not subjected to stroke) receiving W146 are also shown in panel D. PS, saline, and W146 were administered as in panel B. Mean ± SEM; n = 6 mice per group.