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P95 INTRODUCTION: Stimulation of angiogenesis in  ischemic brains may be of major value in stroke therapy. Administration  of vascular endothelial growth factor (VEGF) is considered particularly  effective as an angiogenic factor for hypoxia-related injuries. We  therefore quantitatively compared the effect of VEGF on microvessels of  normal and ischemic brain cortices. Vascular parameters of microvessels  measured included changes in numerical (NA ), volume  (Vv ), surface (Sv ) and length (Lv )  densities along with diameter.METHODS: VEGF165 protein at 1μg/ml was infused into the common carotid artery  of normal and ischemic adult male Sprague-Dawley rats with a  miniosmotic pump for 7 days at 1 μl/hr (VEGF infusion therefore 1  ηg/hr). Animals (n = 3 or 4 per group) were sacrificed at 7 days  post-surgery. Ischemia was induced by occlusion of the middle cerebral  artery for 4 hours. Vascular parameters were quantitated by light  microscopic morphometry. Normal and ischemic brains not infused by VEGF  served as controls.RESULTS: Mean and S.D. of the vascular  parameters (NA [# of vessels/mm2 ]; Vv [%]; Sv [mm2 /mm3 ];  Lv [mm/mm3 ];D [μm]) of the  different groups are as follows: A) Normal brains (462 ± 63;  2.00± 0.2; 13.9 ± 1.7; 925 ± 127; 5.48  ± 0.5) B) Normal brains (480 ± 38; 2.25± 0.3;  14.9 ± 0.8; 961 ± 76; 4.98 ± 0.3) + VEGF C)  Ischemic brains (471 ± 47; 2.06± 0.2; 14.3 ±  1.4; 942 ± 94; 5.11 ± 0.8) D) Ischemic brains (579 ±  102; 2.04 ± 0.3; 16.2 ± 2.7; 1159 ± 205; 4.64 ±  0.4) + VEGF There are no significant differences between the  groups.CONCLUSIONS: Intra-arterial infusion of  VEGF165 protein for 7 days at 1 ηg/hr has no effect on  the vascular parameters of normal or ischemic cortices. Infusion of  VEGF alone may not be sufficient for inducing neovascularization in  intact brain. Further studies specifically testing the appropriate  concentration, duration, VEGF isoform(s), manner of administration  (protein, plasmids or viral vectors), use of combinational angiogenic  factors along with permeability or other side effects are critical to  ascertain the angiogenic merits of VEGF for stroke therapy.

INTRA-ARTERIAL INFUSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN NORMAL AND ISCHEMIC BRAINS HAS NO EFFECT ON ANGIOGENESIS