Abstracts

RATIONALE: In adult rats, adrenalectomy (ADX) results in delayed and highly selective neurodegeneration of dentate granule cells but attenuates kainic acid-induced injury of hippocampal pyramidal cells. Prior seizures evoked by electroshock protect against the ADX-induced granule cell death and ADX performed in P10 rats reduces behavioral inhibition. However, ADX has not been previously attempted during the first postnatal (P) week and the effects of glucocorticosteroid (CORT) depletion on seizures and neuronal injury in this early neonatal period are unknown. Therefore, ADX was performed on P5-P6 pups and sustained seizures with kainate (KA) were induced three times on postnatal ages (P7, P10 and P13).
METHODS: Neonatal rat pups were anesthetized with low doses of ketamine and the initial incision was made along the middle of the back. The surgery scope was exposed with expanders made from paper clips and the adrenals were removed bilaterally with microsurgery instruments. All incisions were sutured with human hair. Sham control operations were performed but without removing the adrenal glands. KA (2 mg/kg ) was used to induce seizures. CORT plasma levels by radioimmunoassay (RIA) and cell injury with classic histological stains were assessed in controls and 48 hrs after ADX and the 3rd KA seizure.
RESULTS: Approximately 95 % of the animals survived the surgery. There were no changes in seizure onset or behavior post ADX and KA at the ages examined relative to controls. No detectable levels of plasma CORT were observed after ADX with RIA. Chromatin and silver stains 6-7 days after ADX or sham operation showed no histological change in the hippocampus or other brain structures. In contrast, in ADX animals with 3 episodes of KA seizures, many thalamic nuclei, particularly those of the midline, showed eosinophilic or argyrophilic deposits within a large number of cell somata. Some injured cells were also revealed in the hippocampal CA3 region; the dentate gyrus was completely spared.
CONCLUSIONS: These observations implicate age-dependent differences in the action of adrenal steroids on neuronal survival within limbic structures involved in seizure propagation.