S13-3. Glial dysfunction and eplileptogenicity

Abstract

Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy, partly characterized by hippocampus sclerosis. Recent accumulating evidence show that changes in glial cells are obvious in TEL, but an involvement of glial changes in TLE is still a matter of debate. Here, we show that status epilepticus (SE) induced activation of microglia, followed by induction of “epileptogenic astrocytes” in the hippocampus. Pilocarpine (Pilo) was used to induce SE in male adult B6 mice. Morphological and functional changes in glia were assessed by immunohistochemical analysis and Ca2+ imaging in the hippocampal slices, respectively. Pilo increased a fast and transient microglial activation (1–3 days after SE), which was followed by sustained activation of astrocytes in the hippocampus (7–28 days after SW). Twenty-eight days after SE, the mice showed susceptibility to Pilo, suggesting induction of epileptogenicity. At this time point, reactive astrocytes displayed excess Ca2+ excitability, reduction of which resulted in inhibition of epileotogenicity. Taken together, after SE, astrocytes become “epileptogenic astrocytes”, whose aberrant Ca2+ excitability should be a cause of epileptogenicity.