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Enhanced angiogenesis and reduced infarct size by vascular endothelial growth factor D is not translated to behavioral outcome in a rat model of ischemic stroke

Pavel Yanev, Jukka Jolkkonen, Kari J. Airenne, Seppo Y Herttuala and Thomas Wirth

Vascular endothelial growth factors (VEGF) induce angiogenesis in experimental stroke models. Robust angio-genic response by VEGF, however, initially creates leaky vessels leading to edema, which may compromise functional recovery. The aim of the present work was to develop adenoviral and baculoviral gene delivery of VEGF-D, a novel member of the VEGF family, to enhance long-term angiogenesis and functional recovery in a photothrombotic model of stroke in rats. Treatment effects were assessed by histology and behavioral testing. The lesion size in the adeno-VEGF-DΔNΔC (p< 0.01) and adeno-VEGF-D (p< 0.05) groups was substantially re-duced compared to vehicle controls. The short form of VEGF-D significantly increased the number of newly formed vessels in the medial (p< 0.001) and lateral cortex (p< 0.05) compared to vehicle controls. Baculo-VEGF-DΔNΔC treated rats showed significant effect in the medial cortex (p< 0.01). The limb placing test showed transient impairment in all virus treated groups compared to the vehicle group at the acute phase 2 and 4 days after operation (p< 0.05). The cylinder test revealed a significant limb-use asymmetry in all ischemic animals at day 7, 14 and 21 after ischemia, which was not affected by VEGF-D treatment. In conclusion, viral mediated gene transfer of VEGF-D induced angiogenesis and reduced infarct size, which were, however, not translated to improved functional outcome in the stroke model used.