Effect of vascular endothelial growth factor (VEGF) on blood‐brain barrier (BBB) permeability of pial arteries vs. parenchymal arterioles

Abstract

Under pathologic conditions, including ischemia and reperfusion, VEGF has been shown to mediate edema formation and contribute to brain injury. In the present study, we compared both cerebral endothelial cell permeability and changes in diameter in response to VEGF between cerebral pial middle cerebral arteries (MCA) and parenchymal arterioles (PA). MCA and PA were dissected from male Wistar rats (n=14) and mounted on glass cannulas within an arteriograph chamber. Vessels were perfused with fluorescent dextran (3000MW), pressurized to either 40mmHg (PA) or 75mmHg (MCA) and both diameter and clearance of dextran/μm2 (permeability) were measured after cumulative addition of VEGF (10–500ng/mL). VEGF had little effect on diameter of MCA or PA; however, both vessel types responded to VEGF by increasing permeability of the BBB. Permeability increased 2-fold in both vessel types at 10ng/mL VEGF, increasing to 8-fold at 500ng/mL VEGF (p<0.01 vs. no VEGF for all concentrations). These results demonstrate that VEGF increases BBB permeability significantly and to a similar extent in pial and parenchymal brain vessels, suggesting that both vessel types have BBB properties and may contribute to enhanced vascular permeability following brain injury. Supported by NS 043316 and Totman Medical Research Trust