A CULTURE MODEL OF REACTIVE ASTROCYTES - INCREASED NERVE GROWTH-FACTOR SYNTHESIS AND REEXPRESSION OF CYTOKINE RESPONSIVENESS

Reactive gliosis, which occurs in response to damage to the central ne rvous system, has been recognized for years but is not yet understood. We describe here a tissue culture model of reactive astrocytes used t o characterize their properties. Cultures are prepared 1 week followin g 6-hydroxydopamine (6-OHDA) lesion of rat substantia nigra and compar ed with astrocytes cultured from normal adult rats or rats injected wi th saline only. Astrocytes from the 6-OHDA-lesioned side contained ele vated levels of glial fibrillary acidic protein (GFAP) and GFAP mRNA a nd were intensely immunoreactive for GFAP, vimentin, and two epitopes that in vivo are found only on reactive astrocytes. The basal content of nerve growth factor (NGF) mRNA and NGF in astrocytes from 6-OHDA-le sioned rats was significantly higher relative to control astrocytes. T wo inflammatory cytokines, interleukin-1 beta and interferon-gamma, in creased synthesis of NGF up to 20-fold in the reactive cells, whereas there was no response in the normal adult astrocytes. Astrocytes from postnatal day 2 rats shared many of the properties of the reactive adu lt astrocytes. These cultures offer the possibility to characterize th e cellular and molecular properties of reactive astrocytes and to dete rmine the factors responsible for activation of astrocytes.