Experimental Models for Astrocyte Activation and Fibrous Gliosis

Abstract

Astrocytes are thought to perform a variety of metabolic and structural functions depending on the developmental, normal, or disease state of the central nervous system (CNS). In response to CNS injury or trauma, astrocytes proliferate and increase in size; their cytoplasmic processes become larger and more tortuous; and there is a substantial increase in the number of intermediate glial filaments and glial fibrillary acidic protein (GFAP) content. The mechanism of reactive GFAP accumulation is an area of active inquiry. It could result from decreased degradation. Rapid proteolytic degradation of GFAP in a continuous human glioma cell line grown in culture and as a solid tumor (1) and in rodent optic nerve and spinal cord has been reported (2, 3). Alternatively, increased synthesis of GFAP, as a result of translation of pre-existing GFAP mRNA, or de novo transcription of GFAP mRNA are possible explanations for this observation. Since glial filament production appears to play a role in CNS scarring and astrocyte differentiation, studies of GFAP activation and of cytoskeletal and metabolic functions of GFAP in astrocytes have been areas of investigation in our laboratory since we first reported and suggested that GFAP was a constituent of glial filaments (4, 5). If reactive fibrous gliosis could be inhibited or delayed in trauma and disease, the other cell types, oligodendroglia and neurons, might have the opportunity to respond and re-establish in a more normal manner; conversely, a highly anaplastic astrocytoma might be induced to differentiate.