Sequential expression of surface antigens and transcription factor NFkappaB 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 kappaB (NFkappaB), were performed. NFkappaB nuclear translocation was controlled and measured using the electrophoretic mobility shift assay. One day after SE, neurodegeneration was obvious in CA3 pyramidal layers; NFkappaB staining in neurons and its translocation to the nucleus enhanced. From day 4 to at least day 8 post-SE, MHC-positive microglia, NFkappaB over-expression in thickened astrocytes, and increased levels of its activated form could be observed. The excitotoxic model caused more severe lesions, but NFkappaB and MHC expression were similar in both models. These results suggest that during long-lasting seizures: (i) neuronal firing activates NFkappaB expression and translocation; (ii) microglia expresses MHC; (iii) astrocytes, probably stimulated by microglial cytokines, over-express NFkappaB, 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.
Lerner-Natoli
M
M
CNRS UPR 9023, Laboratoire de Médecine Expérimentale, Institute de Biologie, Montpellier, France. lerner@ccipe.montp.inserm.fr
Montpied
P
P
Rousset
M C
MC
Bockaert
J
J
Rondouin
G
G
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D001692:Biological Transport; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007267:Injections; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
D000954:Antigens, Surface; D018690:Excitatory Amino Acid Agonists; D016328:NF-kappa B; D009498:Neurotoxins; D007608:Kainic Acid