title: Postischemic steroid modulation: effects on hippocampal neuronal integrity and synaptic plasticity.
abstract: Elimination of corticosteroids after ischemia, by removal of the adrenals, has been reported to preserve neuronal integrity later. To establish the therapeutic potential of this observation, the authors address two questions: first, whether clinically more relevant steroid manipulations after ischemia exert similar protective effects, and second, whether changes in synaptic functioning occur along with structural alterations. To test this, the authors treated animals immediately after hypoxia-ischemia with (1) the steroid synthesis inhibitor metyrapone, (2) the synthetic glucocorticoid receptor agonist dexamethasone, (3) the selective glucocorticoid antagonist RU 38486, or (4) corticosterone. Metyrapone, but none of the other compounds, attenuated 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. None of the other experimental treatments influenced the impaired synaptic function. Gross morphologic analysis revealed no differences in the loss of neuronal structure between the experimental groups at this time point. Taken together, these data suggest that metyrapone preserves neuronal functioning despite loss of neuronal structure. The authors tentatively conclude that preventing the ongoing production of steroids shortly after ischemia can delay and attenuate the appearance of ischemia-related pathology.
authors.affiliation: Institute for Neurobiology, Graduate School for Neurosciences, University of Amsterdam, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Krugers
authors.forename: S
authors.initials: S
authors.lastname: Maslam
authors.forename: S M
authors.initials: SM
authors.lastname: Van Vuuren
authors.forename: J
authors.initials: J
authors.lastname: Korf
authors.forename: M
authors.initials: M
authors.lastname: Joëls
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006624:Hippocampus / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D006727:Hormone Antagonists / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000032:analysis; D015735:Mifepristone / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005938:Glucocorticoids; D006727:Hormone Antagonists; D008869:Microtubule-Associated Proteins; D015735:Mifepristone; D003907:Dexamethasone; D003345:Corticosterone; D008797:Metyrapone