VEGF enhances angiogenesis and promotes blood-brain barrier leakage in theischemic brain

VEGF is a secreted mitogen associated with angiogenesis and is also a poten t vascular permeability factor. The biological role of VEGF in the ischemic brain remains unknown. This study was undertaken to investigate whether VE GF enhances cerebral microvascular perfusion and increases blood-brain barr ier (BBB) leakage in the ischemic brain. Using magnetic resonance imaging ( MRI), three-dimensional laser-scanning confocal microscope, and functional neurological tests, we measured the effects of administrating recombinant h uman VEGF(165) (rhVEGF(165)) On angiogenesis, functional neurological outco me, and BBB leakage in a rat model of focal cerebral embolic ischemia. Late (48 hours) administration of rhVEGF(165) to the ischemic rats enhanced ang iogenesis in the ischemic penumbra and significantly improved neurological recovery. However, early postischemic (1 hour) administration of rhVEGF(165 ) to ischemic rats significantly increased BBB leakage, hemorrhagic transfo rmation, and ischemic lesions. Administration of rhVEGF(165) to ischemic ra ts did not change BBB leakage and cerebral plasma perfusion in the contrala teral hemisphere. Our results indicate that VEGF can markedly enhance angio genesis in the ischemic brain and reduce neurological deficits during strok e recovery and that inhibition of VEGF at the acute stage of stroke may red uce the BBB permeability and the risk of hemorrhagic transformation after f ocal cerebral ischemia.