Postischemic steroid modulation: Effects on hippocampal neuronal integrityand synaptic plasticity

Elimination of corticosteroids after ischemia, by removal of the adrenals, has been reported to preserve neuronal integrity later. To establish the th erapeutic potential of this observation, the authors address two questions: first, whether clinically more relevant steroid manipulations after ischem ia exert similar protective effects, and second, whether changes in synapti c functioning occur along with structural alterations. To test this, the au thors treated animals immediately after hypoxia-ischemia with (1) the stero id synthesis inhibitor metyrapone, (2) the synthetic glucocorticoid recepto r agonist dexamethasone, (3) the selective glucocorticoid antagonist RU 384 86, or (4) corticosterone. Metyrapone, but none of the other compounds, att enuated the occurrence of seizures immediately after ischemia. Twenty-four hours after hypoxia-ischemia, CAI hippocampal field potentials in response to stimulation of Schaffer/commissural fibers were found to be reduced. The attenuation of synaptic transmission was partly prevented by metyrapone. N one of the other experimental treatments influenced the impaired synaptic f unction. Gross morphologic analysis revealed no differences in the loss of neuronal structure between the experimental groups at this time point. Take n together, these data suggest that metyrapone preserves neuronal functioni ng despite loss of neuronal structure. The authors tentatively conclude tha t preventing the ongoing production of steroids shortly after ischemia can delay and attenuate the appearance of ischemia-related pathology.