Sequential expression of surface antigens and transcription factor NF kappa B by hippocampal cells in excitotoxicity and experimental epilepsy

Neurodegeneration and gliosis have been extensively described after long-la sting seizures; evidence for cytokine involvement in neuron-glia interactio ns does exist. We have therefore studied the hippocampal expression of mole cules responsible for immune and inflammatory reactions, at different time- points following either experimental status epilepticus (SE) or direct exci totoxic damage. Experiments consisting of immunohistochemical labeling of g lial markers, major histocompatibility complex (MHC) and nuclear factor kap pa B (NF kappa B), were performed. NF kappa B nuclear translocation was con trolled and measured using the electrophoretic mobility shift assay. One da y 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-ex pression in thickened astrocytes, and increased levels of its activated for m could be observed. The excitotoxic model caused more severe lesions, but NF kappa B and MHC expression were similar in both models. These results su ggest that during long-lasting seizures: (i) neuronal firing activates NF k appa B expression and translocation; (ii) microglia expresses MHC; (iii) as trocytes, probably stimulated by microglial cytokines, over-express NF kapp a B, the activation of which induces a cascade of reactions, particularly t he transcription of cytokines and/or neuroprotective molecules. Further cla rification of the toxic or protective consequences of delayed inflammatory responses may be interesting in therapy of epilepsy. (C) 2000 Elsevier Scie nce B.V. All rights reserved.