The preparation of the acute brain slice and the artificial environment in which the slice is kept are expected to trigger inflammatory processes. The purpose of the present study is to explore how fast, and to what extent, inflammatory processes are activated in the acute hippocampal slice and whether synaptic and astrocytic functions are affected. We use immunohistochemical and electrophysiological methods to compare control slices at different times after the preparation with slices exposed to pro-inflammatory mediators such as Lipopolysaccaride (LPS) and Interleukin 1(IL-1). We show that markers of activated microglia, ED1 and Iba1, are up regulated with time in the acute slice preparation, with and without the addition of LPS. Furthermore, we have found that astrocyte mediated short-term synaptic depression is abolished after 7–10 hours in the recording chamber whilst field excitatory postsynaptic potentials remain unaltered, suggesting that astrocyte functions are more sensitive to slice aging than synaptic transmission. We conclude that some inflammatory markers develop with time in the acute brain slice, and suggest that a beginning inflammation might explain the time related decline in astrocyte mediated short term synaptic depression.