LONG-TERM PRODUCTION OF NEUROTROPHIC FACTORS BY ASTROCYTE CULTURES FROM HEMIPARKINSONIAN RAT-BRAIN

Transplantation of dopaminergic or neurotrophic tissues is an experime ntal treatment of Parkinson's Disease. However, in animal models susta ined recovery may occur after surgical trauma to affected brain areas even in the absence of grafted tissue. Consequently, brain tissue reac ting to local trauma in these experiments must be capable of substanti al neurotrophic responses. To evaluate the potential of astrocytes in these neurotrophic responses, cultures were obtained from gelatin impl ants into striatal cavities that were created in hemiparkinsonian rats . The type 1 astrocyte phenotype as determined immunocytochemically wa s maximal at day 7 in vitro and paralleled the glial reaction in the a djacent brain parenchyma. Neurite-promoting activity of the culture me dium was determined in a chick dorsal root ganglion bioassay and also was established by 7 days. Nerve growth factor antibodies neutralized only around 40% of this activity. Neurotrophic activity was absent wit h assay of media from early or long-term newborn rat astrocytes, and o f medium conditioned by a monoyte/macrophage cell line. Passage after several months yielded astrocyte cultures that repeated a surge of neu rite-promoting activity. This long-term potential to produce multiple neurotrophic factors indicates that autologous astrocytes in affected brain regions may serve either as targets for or agents of therapy of Parkinsonism. (C) 1995 Wiley-Liss, Inc.