GLUCOCORTICOIDS AND THE PREVENTION OF HYPOXIC-ISCHEMIC BRAIN-DAMAGE

We have shown repeatedly that pre-treatment of neonatal rats with dexa methasone provides protection against hypoxic-ischemic brain damage. A lthough the mechanism of action is not certain, hypothermia, an altera tion in cerebral perfusion or an induction of antioxidant enzymes does not readily explain this effect. A relative hyperglycemia is usually observed during hypoxia-ischemia in dexamethasone treated animals, and may provide partial protection, but does not account for the entire r esponse. However, the protective effect is likely mediated by glucocor ticoid receptors since alternate glucocorticoids such as methyl predni solone and corticosterone are also effective. Furthermore, the effect can be inhibited by pre-treatment with a glucocorticoid antagonist RU3 8486. The neuroprotection also appears to be related to alterations in cerebral metabolism. Glucose utilization is reduced prior to hypoxia- ischemia in dexamethasone compared to vehicle treated animals and is b etter maintained during hypoxia-ischemia in dexamethasone treated anim als. In addition, preliminary studies indicate that high energy phosph ates in the brain are higher in dexamethasone treated animals. Thus, g lucocorticoids may provide their protection against hypoxic-ischemic d amage by decreasing basal metabolic energy requirements and/or increas ing the availability or efficiency of use of energy substrates. Crown Copyright (C) 1997 Published by Elsevier Science Ltd. All rights reser ved.