FIGURE 6

Effect of monocyte chemoattractant protein-1 (MCP-1) on blood−brain barrier (BBB) permeability in the absence of chemotactic cytokine receptor 2 (CCR2). CCR2+/+ or CCR2-/- mice received a single injection of MCP-1 (25 g) or a long-term infusion (5 g/h). Monocyte chemoattractant protein-1 was administered by intracerebral administration. Controls received only PBS. Fluorescein isothiocyanate (FITC)-albumin extravasation was examined 12 h after the acute injection and 3 days after the onset of the long-term infusion. In (A), the degree of FITC-albumin extravasation was measured on brain sections and representative reconstructed sections from CCR2+/+ and CCR2-/- mice are shown. Reduced FITC-albumin extravasation was observed in CCR2-/- mice treated with MCP-1 compared with CCR-2 +/+ mice treated in the same way. This observation was confirmed by quantitative analysis of extravasation (E(f)). Values are meanss.d. ‡ and # indicate a significant difference between control and MCP-1-treated CCR2+/+ and CCR2-/-mice at the P<0.05 and P<0.001 level; ^*** indicates a significant difference between CCR2-/- and CCR2+/+ mice at the P< 0.001 level. Scale bar=1000 m. In (B), a PS product was determined to quantify the degree of FITC-albumin extravasation into the ipsi- and contralateral hemispheres. Again, the MCP-1-induced increase in PS product found in CCR2+/+ mice was absent in CCR2-/- mice. Values are meanss.d. ^*** and ^** indicate a significant difference between CCR2-/- and CCR2+/+ mice at the P< 0.001 and P<0.01 level, respectively; # indicates a significant difference between ipsilateral hemisphere of control and MCP-1-treated CCR2-/- and CCR2+/+ mice at the level P<0.001.