OPPOSING EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA-1 ON GLUTAMATE NEUROTOXICITY

Activation of microglia has been emphasized as a critical step in the pathophysiology of degenerative and inflammatory processes of the CNS. Activated microglia release low molecular weight compounds, such as e xcitatory amino acids, that are directly toxic to neurons. Here we dem onstrate that a microglia-derived cytokine, transforming growth factor -beta 1, directly alters the susceptibility of neurons to glutamate-in duced cell damage. Transforming growth factor-beta 1 acts as a neuropr otectant following short-term exposure to glutamate, whereas, followin g chronic exposure to glutamate, similar concentrations of transformin g growth factor-beta 1 actually potentiate excitotoxic cell death. Thi s complex interaction may play an important role in determining the ex tent of local tissue damage.