Astrocytes prevent neuronal death induced by reactive oxygen and nitrogen species

Reactive oxygen and nitrogen species (RO/NS) such as nitric oxide (NO), hyd roxyl radical (OH .), and superoxide anion (O-2(-)) are generated in a vari ety of neuropathological processes and damage neurons. In the present study , we investigated the neuroprotective effects of rat astrocytes against RO/ NS-induced damage using neuron-glia cocultures, and the effects were compar ed to those of microglial cells. Sodium nitroprusside (SNP), 3-morpholinosy dnonimine (SIN-1), and FeSO4 were used to generate NO, O-2(-) and NO, and O H ., respectively. Solely cultured neurons, which were transiently exposed to these agents, degenerated, possibly through apoptotic mechanisms as reve aled by in situ detection of DNA fragmentation, whereas neurons cocultured with either astrocytes or microglial cells were viable even after exposure to RO/NS. In contrast, most neurons cocultured with meningeal fibroblasts d egenerated. Astrocyte-conditioned medium partially attenuated RO/NS-induced neuronal damage. When neurons were cultured on astrocyte-derived extracell ular matrix (AsECM), neuronal death induced by SNP and FeSO4 was almost com pletely inhibited. AsECM contained significant amounts of laminin and fibro nectin, and pure fibronectin and laminin also protected neurons against RO/ NS-induced damage in the same manner as AsECM. These results suggest that a strocytes can protect neurons against RO/NS-induced damage by secreting sol uble and insoluble factors. (C) 1999 Wiley-Liss, Inc.