Expression of vascular endothelial growth factor by reactive astrocytes and associated neoangiogenesis

Injury to the central nervous system (CNS) invokes a reparative response kn own as astrogliosis, characterized largely by hypertrophy, proliferation an d increased expression of glial fibrillary acidic protein (GFAP), resulting in reactive astrocytosis. Based on our prior observation that peritumoral reactive astrocytes express Vascular Endothelial Growth Factor (VEGF), a hi ghly potent and specific angiogenic growth factor, we have hypothesized tha t reactive astrocytosis also contributes to the neovascularization associat ed with astrogliosis. To evaluate this hypothesis we evaluated human surgic al/autopsy specimens from a variety of CNS disorders that induce astroglios is and an experimental CNS needle injury model in wild type and GFAP:Green Fluorescent Protein (GFP) transgenic mice. Using computer image semi-quanti tative analysis we evaluated the number of GFAP-positive reactive astrocyte s, degree of VEGF expression by these astrocytes, associated Factor VIII-po sitive microvascular density (MVD) and Ki-67 proliferating endothelial cell s. The degree of reactive astrocytosis correlated to levels of VEGF immunor eactivity and MVD in the neuropathological specimens. The mouse-needle-stic k brain injury model demonstrated this correlation was temporally and spati ally related and maximal after I week. These results, involving both human pathology specimens augmented by experimental animal data: supports our hyp othesis that the neoangiogenesis associated with reactive astrogliosis is c orrelated to increased reactive astrocytosis and associated VEGF expression . (C) 2000 Elsevier Science B.V. All rights reserved.