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

• Published in: Brain research Vol. 883; no. 1; pp. 87 - 97
• Main Authors: Salhia, Bodour, Angelov, Lilyana, Roncari, Luba, Wu, Xiaoli, Shannon, Patrick, Guha, Abhijit
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 10.11.2000; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Astrocytes - metabolism; Astrocytes - pathology; Astrogliosis; Biological and medical sciences; Brain Diseases - pathology; Brain Diseases - physiopathology; Brain Injuries - pathology; Brain Injuries - physiopathology; Endothelial Growth Factors - metabolism; Fundamental and applied biological sciences. Psychology; GFAP; Glial Fibrillary Acidic Protein - genetics; Gliosis - pathology; Green Fluorescent Proteins; Humans; Indicators and Reagents; Isolated neuron and nerve. Neuroglia; Luminescent Proteins - genetics; Lymphokines - metabolism; Mice; Mice, Transgenic - genetics; Microvascular density; Needlestick Injuries - pathology; Needlestick Injuries - physiopathology; Neoangiogenesis; Neovascularization, Pathologic; Reactive astrocytes; Time Factors; Tissue Distribution; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; VEGF; Vertebrates: nervous system and sense organs; Astrogliosis; Microvascular density; VEGF; Reactive astrocytes; Neoangiogenesis; Cellular and molecular biology; GFAP; Angiogenesis; Vascular endothelium growth factor; Gliosis; Neuroglia; Glial fibrillary acidic protein; Astrocyte; Gene expression
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)02825-0

Injury to the central nervous system (CNS) invokes a reparative response known as astrogliosis, characterized largely by hypertrophy, proliferation and 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 highly potent and specific angiogenic growth factor, we have hypothesized that reactive astrocytosis also contributes to the neovascularization associated with astrogliosis. To evaluate this hypothesis we evaluated human surgical/autopsy specimens from a variety of CNS disorders that induce astrogliosis and an experimental CNS needle injury model in wild type and GFAP:Green Fluorescent Protein (GFP) transgenic mice. Using computer image semi-quantitative analysis we evaluated the number of GFAP-positive reactive astrocytes, degree of VEGF expression by these astrocytes, associated Factor VIII-positive microvascular density (MVD) and Ki-67 proliferating endothelial cells. The degree of reactive astrocytosis correlated to levels of VEGF immunoreactivity and MVD in the neuropathological specimens. The mouse–needle–stick brain injury model demonstrated this correlation was temporally and spatially related and maximal after 1 week. These results, involving both human pathology specimens augmented by experimental animal data, supports our hypothesis that the neoangiogenesis associated with reactive astrogliosis is correlated to increased reactive astrocytosis and associated VEGF expression.