Down-regulation of the hypothalamo-pituitary-adrenal axis reduces brain damage and number of seizures following hypoxia/ischaemia in rats.

Several reports suggest that the activity of the hypothalamo-pituitary-adrenal axis (HPA-axis) is increased following hypoxia/ischaemia and that this might be associated with increased neuronal vulnerability. The main goal of this study was to examine the effects of down-regulation of the HPA-axis on the hypoxia/ischaemia-induced (1) rise of plasma corticosterone levels, (2) seizures, and (3) brain damage. Down-regulation of the HPA-axis was induced by prolonged corticosterone treatment lasting until 24 h before hypoxia/ischaemia exposure. When compared to 8 days vehicle (sesame oil)-treated animals (CONT), 8 days daily corticosterone (40 mg/animal)-treated animals (CORT) showed significantly reduced adrenal-and thymus weight. Shortly after hypoxia/ischaemia plasma corticosterone levels in CORT animals were significantly reduced (17.30 micrograms/dl +/- 3.50) when compared to CONT animals (54.80 micrograms/dl +/- 7.78). This correlated with the brain damage which is expressed as the ratio between the damaged area and the total area. The total brain damage was significantly less in CORT-treated animals (28% +/- 11%) than in CONT animals (69% +/- 2%). Following hypoxia/ischaemia the number of seizures was significantly reduced in CORT animals (56 +/- 26) when compared to CONT animals (217 +/- 50). We conclude that prolonged corticosterone treatment resulting in down-regulation of the HPA-axis leads to (1) lower plasma corticosterone levels during hypoxia/ischaemia, (2) a reduction in brain damage following hypoxia/ischaemia, and (3) less hypoxia/ischaemia-induced seizures.