Duration of resealing using multidose regimens of VA64 given intravenously (IV), intravenously plus intracerebroventricularly (IV/ICV), or as an intravenous bolus (20 mL/kg) followed by continuous infusion of 20 mL/kg/h × 2 hours (IV Cont). Mice were subjected to controlled cortical impact and administered YOYO-1 at 1 hour, followed 5 minutes later by the first dose of VA64 and 5 minutes later by PI. VA64 was administered every 30 minutes IV or IV+ICV after the initial dose for a total of four doses over 90 minutes. Mice were euthanized and brains obtained for analysis of membrane resealing at 120 minutes after the initial dose of IV or IV/ICV VA64. In continuous infusion groups, brains were obtained after the end of the 2-hour IV infusion of VA64. (A–C) Representative photomicrographs of YOYO-1+ and PI+ cells from the IV VA64 administration group. Note the lack of membrane resealing. (D) Quantitative analyses of membrane resealing by the three different multiple-dose paradigms. *P<0.03 IV Cont (n=5) versus IV MD (IV multiple dose, n=5) and IV/ICV (n=7) paradigms. Scale bar=100 μm.