Glucocorticoids exacerbate insult-induced declines in metabolism in selectively vulnerable hippocampal cell fields

Glucocorticoids (GCs), the adrenal steroids released during stress, can com promise the ability of hippocampal neurons to survive necrotic neurological insults. This GC-induced endangerment has energetic facets, in that it can be attenuated with energy supple mentation. In the present report, we stud ied the effects of GCs on the metabolic response of specific hippocampal ce ll fields to necrotic insults. We used silicon microphysiometry, which allo ws indirect measurement of metabolism in real time in tissue explants. Agly cemia caused a significant decline in metabolism in dentate gyms explants, but not in CA1 or CA3 explants. When coupled with our prior report of cyani de disrupting metabolism only in CA1 explants, and the glutamatergic excito toxin kainic acid disrupting metabolism only in CA3 explants, this demonstr ates that microphysiometry can detect the selective regional vulnerability that characterizes the hippocampal response to these necrotic insults. We t hen examined the effects of GCs on the response to these insults, monitorin g explants taken from rats that were adrenalectomized, intact, or treated w ith corticosterone (the GC of rats) that produced circulating levels equiva lent to those of major stressors. Increased exposure to GCs worsened the de cline in metabolism in dentate gyrus explants induced by hypoglycemia, and in CA1 explants induced by cyanide (after eliminating the effects of glial release of lactate for the support of neuronal metabolism). Thus. GCs worse n the metabolic consequences of necrotic insults in hippocampal explants. ( C) 2000 Elsevier Science B.V. All rights reserved.