Vascular endothelial growth factor stimulates Schwann cell invasion and neovascularization of acellular nerve grafts

The aim of this study was to investigate the effects of vascular endothelia l growth factor (VEGF) on regeneration of the rat sciatic nerve in vivo. To that end we used 10-mm long cell-free nerve grafts to bridge a gap in the sciatic nerve. The grafts were pretreated with either VEGF (50, 100 or 250 ng/ml), nerve growth factor(NGF, 100 ng/ml) or laminin (100 ng/ml) before i mplantation. Outgrowth of axons, Schwann cells, blood vessels and macrophag es were studied 10 days post-implantation by the use of immunocytochemistry and histochemistry. Grafts pretreated with VEGF stimulated the outgrowth o f Schwann cells and blood vessels but not axons. In such grafts, the Schwan n cells also exhibited a dramatic change in morphology and became filled wi th large lipid-containing vacuoles. These cells also showed an intense immu noreactivity for the VEGF receptor flk-1. Neither pretreatment with laminin nor NGF affected the outgrowth of Schwann cells. However, NGF treatment in creased the number of axons in the graft but was not able to counteract inj ury-induced downregulation of substance P in the dorsal root ganglia. The r esults show that local application of VEGF promotes at least two events, in vasion of Schwann cells and neovascularization, which are important during nerve regeneration. The findings suggest that the effects of the pretreatme nt by the growth factors is local and limited to the graft, whereas central events like neuropeptide synthesis is not affected. (C) 1999 Published by Elsevier Science B.V. All rights reserved.