Long-term production of neurotrophic factors by astrocyte cultures from hemiparkinsonian rat brain.

Transplantation of dopaminergic or neurotrophic tissues is an experimental treatment of Parkinson's Disease. However, in animal models sustained recovery may occur after surgical trauma to affected brain areas even in the absence of grafted tissue. Consequently, brain tissue reacting to local trauma in these experiments must be capable of substantial neurotrophic responses. To evaluate the potential of astrocytes in these neurotrophic responses, cultures were obtained from gelatin implants into striatal cavities that were created in hemiparkinsonian rats. The type 1 astrocyte phenotype as determined immunocytochemically was maximal at day 7 in vitro and paralleled the glial reaction in the adjacent brain parenchyma. Neurite-promoting activity of the culture medium 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 with assay of media from early or long-term newborn rat astrocytes, and of medium conditioned by a monoyte/macrophage cell line. Passage after several months yielded astrocyte cultures that repeated a surge of neurite-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.