Interrelations between nuclear-factor kappa B activation, glial response and neuronal apoptosis in gerbil hippocampus after ischemia

Abstract

Spatial and temporal relations between transcriptional factor NFκB activation and glia reaction in gerbil hippocampus after transient cerebral ischemia has been studied. Activation of protein binding to NFκB consensus oligonucleotide was determined by electrophoretic mobility gel shift assay (EMSA) in homogenates from dorsal (DP- an equivalent of CA1 sector) and abdominal (AbP- containing CA2-4 and gyrus dentatus) parts of hippocampus. A significant activation of NFκB binding was observed exclusively in DP as early as 3 h after ischemia and at this tinge that response preceded any other morphological signs of postischemic tissue injury. This early enhancement of NFκB binding was followed by microglia activation visualized in CA1 pyramidal region at 24 h of recovery by histochemical staining with lectin from Ricinus communis (RCA-120). Simultaneously, only a moderate increase of immunostaining against glial fibrillary acidic protein (GFAP) was observed homogeneously in all parts of hippocampus. This uniform pattern of astrogliosis was preserved until postischemic day 3-4, when apoptotic DNA fragmentation in CA1 pyramidal neurons had been clearly documented by TUNEL staining. At this period however, continuous elevation of NFκB binding in DP corresponded with similar response manifested also in AbP of the hippocampus. These results evidence a preferential NFκB involvement in an early microglia activation in the apoptogenic CA1 sector, although its role in a later astrocytic response to ischemia could not be neglected too.