Sequential expression of surface antigens and transcription factor NFκB by hippocampal cells in excitotoxicity and experimental epilepsy

Neurodegeneration and gliosis have been extensively described after long-lasting seizures; evidence for cytokine involvement in neuron-glia interactions does exist. We have therefore studied the hippocampal expression of molecules responsible for immune and inflammatory reactions, at different time-points following either experimental status epilepticus (SE) or direct excitotoxic damage. Experiments consisting of immunohistochemical labeling of glial markers, major histocompatibility complex (MHC) and nuclear factor kappa B (NF kappa B), were performed. NF kappa B nuclear translocation was controlled and measured using the electrophoretic mobility shift assay. One day after SE, neurodegeneration was obvious in CA3 pyramidal layers; NF kappa B staining in neurons and its translocation to the nucleus enhanced. From day 4 to at least day 8 post-SE, MHC-positive microglia, NF kappa B over-expression in thickened astrocytes, and increased levels of its activated form could be observed. The excitotoxic model caused more severe lesions, but NF kappa B and MHC expression were similar in both models. These results suggest that during long-lasting seizures: (i) neuronal firing activates NF kappa B expression and translocation; (ii) microglia expresses MHC; (iii) astrocytes, probably stimulated by microglial cytokines, over-express NF kappa B, the activation of which induces a cascade of reactions, particularly the transcription of cytokines and/or neuroprotective molecules. Further clarification of the toxic or protective consequences of delayed inflammatory responses may be interesting in therapy of epilepsy. (C) 2000 Elsevier Science B.V. All rights reserved.