Glucocorticoids and hippocampal damage

Evidence that damage to neurons of the hippocampus is among the deleterious effects of chronic GC-exposure is presented, and studies suggest that GC administration in the aftermath of hypoxia-ischemia or seizure may worsen hippocampal damage, while attentuation of endogenous GC secretion at that time might well prove protective of the structure.

Abstract

Glucocorticoids (GCs) are secreted by the adrenal gland and mediate numerous adaptations to acute stress. Because many of these adaptations are catabolic in nature, prolonged GC exposure can ultimately be deleterious. This review presents evidence that damage to neurons of the hippocampus is among the deleterious effects of chronic GC-exposure. The hippocampus is a principal neural target tissue for the steroids, with high concentrations of GC receptors. The rate of hippocampal neuron loss appears sensitive to cumulative GC exposure over the lifespan: decreased concentrations retard senescent neuron loss while chronic exposure accelerates the process. The extent of this loss after acute insults such as hypoxia-ischemia or excitotoxic seizures is simularly sensitive to GC concentrations. GCs appear to induce a general metabolic vulnerability in hippocampal neurons, impairing their capacity to survive varied insults. This GC action occurs directly, rather than secondarily to peripheral GC actions; moreover, the pattern is GC-specific, as non-GC steroids do not potentiate the damage of hippocampal insults. Finally, an important component of the phenomenon may involve the inhibition of hippocampal neuronal glucose uptake by GCs, leaving neurons more vulnerable to any coincident metabolic challenges. These studies suggest that GC administration in the aftermath of hypoxia-ischemia or seizure may worsen hippocampal damage, while attentuation of endogenous GC secretion at that time might well prove protective of the structure.