VEGF mRNA and its receptor flt-1 are expressed in reactive astrocytes following neural grafting and tumor cell implantation in the adult CNS

Abstract

Significant angiogenesis occurs only after injury in the adult mammalian brain; capillaries proliferate and astrocytes are activated by presently unresolved cellular mechanisms. Because of the intimate relationship between astrocytes and brain capillaries we examined the expression of the specific endothelial mitogen vascular endothelial growth factor (VEGF) in reactive astrocytes following CNS trauma models: neural grafting, stab wounds, and glioma implantation. In situ hybridization was combined with GFAP immunohistochemistry to delineate VEGF mRNA expression in reactive astrocytes. In addition, VEGF and its receptor flt-1 protein expression were detected immunohistochemically. In all three models we found unexpectedly that only reactive astrocytes, not endothelium, expressed the VEGF receptor flt-1, VEGF mRNA, and VEGF protein in a spatiotemporal manner, suggesting that activated astroglia may have a direct role in the induction of angiogenesis or permeability in mature brain. In addition, secreted VEGF may play a part in astroglial signalling by the induction of its own receptor in reactive astroglia following injury. These findings may have significant implications with regard to growth and reparative mechanisms of the adult cerebrovasculature.