Microglia, in response to cytokines, demonstrate a number of enhanced biochemical and functional properties which reflect a state of activation. In this study, we evaluated the ultrastructural alterations of murine microglia that were associated with activation by interferon-gamma (IFN-gamma) plus tumor necrosis factor-alpha (TNF-alpha). Microglial cell culture treated with these cytokines generated significant amounts of the free radical nitric oxide (NO), a biochemical marker of activation. Correlative transmission (TEM) and scanning (SEM) electron microscopic analyses of these cytokine-activated microglia demonstrated two prominent features: proliferation of cell processes and increased formation of membrane bound dense bodies typical of lysosomes. Since activated microglia have been implicated in the pathogenesis of a number of neurodegenerative diseases, application of the ultrastructural findings in the in vitro study may prove useful in determining the state of activation of microglia in brain specimens from patients with these neurological disorders.

The mechanism underlying meningitis-associated brain injury is unclear. This study investigated the hypothesis that lipopolysaccharide (LPS) alters astrocyte function and structure via the release of proinflammatory cytokines. In enriched murine astrocyte cultures, LPS inhibited (P < 0.05) glutamine synthetase activity, 3H-gamma aminobutyric acid uptake, and DNA synthesis; LPS also induced ultrastructural changes. Antibodies to tumor necrosis factor-alpha, interleukin-1, and interleukin-6 blocked (P < 0.05) in part the LPS-induced inhibition of astrocyte function. Also, treatment of astrocyte cultures with cytokines significantly altered these astrocyte functions and ultrastructure. Taken together, the present findings support the hypothesis that LPS affects astrocyte function and structure via the release of proinflammatory cytokines, especially tumor necrosis factor-alpha.

The role of microglia in host defense against Toxoplasma gondii is unknown. In the present study, we investigated the multiplication of T. gondii tachyzoites in murine microglial cell cultures. T. gondii multiplied readily in these cells; multiplication was prevented when microglia were activated with interferon-gamma plus lipopolysaccharide, a treatment that also upregulates nitric oxide (NO) synthase activity. Simultaneous treatment of microglial cell cultures with activation signals and the NO synthase inhibitor NG-monomethyl-L-arginine (NGMA) prevented the antitoxoplasmic activity. Transmission electron microscopic analysis demonstrated degenerative tachyzoites in activated microglia but not in control or NGMA groups. These findings support the view that the host defense function of activated microglia against T. gondii involves generation of the free radical NO.