In the present study to evaluate the effects of ischemia on sodium-potassium adenosine triphosphatase (Na(+)-K+ ATPase) alpha1 subunit (alpha6F) expression in the glia, the immunodensities of both Na(+)-K+ ATPase and the glial fibrillary acidic protein in the hippocampus were measured and analyzed. In the sham hippocampus, alpha6F immunoreactivity was mainly observed in the both the molecular layer and the polymorphic layer of dentate gyrus. At 30 min after ischemic insult, the alpha6F immunoreactivity was markedly decreased in the molecular layer of the dentate gyrus, in contrast to the appearance of this immunoreactivity in the hilar neurons. Up to 12 h after ischemic insult, the alpha6F immunoreactivity was re-enhanced in the molecular layer of dentate gyrus. In addition, the alpha6F immunoreactivity appeared slightly in the glial components in the hippocampal region. Four days after ischemia-reperfusion, the intensity of alpha6F immunoreactivity in the glial cells was highest. At this time point, strong alpha6F immunoreactivity was colocalized with GFAP immunoreactivity in the strata radiatum of the CA1 and the molecular layer of the dentate gyrus. These results suggest that the enhancement of alpha6F immunoreactivity may be a compensatory response to regulate the ion homeostasis in the brain. In addition, the maintenance of Na(+)-K+ ATPase activity in the astrocytes may explain the resistant characteristics of these cells to ischemic insults.