Figure 1.
The pharmacological blockade or genetic elimination of adenosine A2AR prevents hippocampal damage caused by either amygdala kindling or kainate administration, while only attenuating the evolution of convulsions. A, Male Wistar rats were implanted with electrodes in the amygdala and stimulation twice daily progressively increased the severity of convulsions until triggering a fully kindled state (n = 7), which was reduced by a selective A2AR antagonist SCH58261 (0.05 mg twice daily; n = 8). B, Rats were killed 5 d after reaching fully kindled state and only the kindled rats treated with saline displayed degenerated cells, identified by FluoroJade-C labeling, in all hippocampal fields, whereas neither control nor SCH58261-treated rats, irrespective of being kindled or not, displayed FluoroJade-C staining. C, On intraperitoneal administration of kainate (KAI, 10 mg/kg; n = 11), rats treated with 0.05 mg/kg of SCH58261 (KAI+SCH, n = 12) displayed a similar pattern of acute convulsions (within 15 min and lasting no >75 min after KAI). D, However, SCH58261 prevented the histologic modifications observed in the hippocampus 24 h after kainate administration, namely, the dispersion of pyramidal cell layer with Nissl staining, the appearance of ruptured cells stained with FluoroJade-C (FJ-C), the modification of microglia staining with tomato lectin, and the increase of the number and density of GFAP-stained element compatible with astrogliosis. E, F, The administration of kainate (35 mg/kg, sc) to wild-type (WT) C57Bl6 mice (n = 11) triggered a convulsive period followed by the appearance of degenerated cells stained with FluoroJade-C together with a microgliosis and astrogliosis concluded from the altered staining of hippocampal sections with CD11b and GFAP, respectively; notably, the same exposure to kainate (+K) of littermates with a genetic deletion of A2AR (A2AR-KO, gKO) triggered a similar intensity of convulsions, which did not evolve into an evident pattern of neurodegeneration, microgliosis, or astrogliosis in the hippocampus after 24 h (n = 10). Calibration bars in each photograph are 100 µm, except the insets, which display higher magnifications of either astrocytes or microglia (calibration bar = 10 µm). Data are mean ± SEM; *p < 0.05 between bars or versus control (saline).