CORTICOSTERONE EXACERBATES CYANIDE-INDUCED CELL-DEATH IN HIPPOCAMPAL CULTURES - ROLE OF ASTROCYTES

Previous study demonstrated that, in hippocampal neuron/glia mixed cul tures, glucocorticoids (GCs) enhanced extracellular overflow of [H-3]D -aspartate ([H-3]D-Asp) by decreasing its uptake, thereby aggravating cell death during cyanide-induced ischemia. Since neuronal and glial c ells respond to ischemic insult and GC differently, this study further evaluated the relative significance of these cells in GC endangering ischemic cell death. Using D-[2,3-H-3]aspartic acid ([H-3]D-Asp) as a tracer, it was found that corticosterone (CORT, the physiological GC i n rat) enhanced the overflow of extracellular [3H]D-Asp in astrocyte c ultures and, to a lesser extent, in neuron-enriched cultures during cy anide-induced ischemia. Analysis of [H-3]D-Asp uptake kinetics indicat es that CORT reduced the maximum uptake rate in cultured astrocyte, bu t not in neurons, after cyanide exposure. It is concluded that, during cyanide-induced ischemia, CORT might mainly impair the ability of ast rocytes to clear excitatory amino acids from the synapse, thus exacerb ating the damaging cascade of these amino acids. (C) 1998 Elsevier Sci ence Ltd. All rights reserved.