Glucocorticoids and the prevention of hypoxic-ischemic brain damage

We have shown repeatedly that pre-treatment of neonatal rats with dexamethasone provides protection against hypoxic-ischemic brain damage. Although the mechanism of action is not certain, hypothermia, an alteration 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 response. However, the protective effect is likely mediated by glucocorticoid receptors since alternate glucocorticoids such as methyl prednisolone and corticosterone are also effective. Furthermore, the effect can be inhibited by pre-treatment with a glucocorticoid antagonist RU38486. 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 animal and is better maintained during hypoxia-ischemia in dexamethasone treated animals. In addition, preliminary studies indicate that high energy phosphates in the brain are higher in dexamethasone animals. Thus, glucocorticoids may provide their protection against hypoxic-ischemic damage by decreasing basal metabolic energy requirements and/or increasing the availability or efficiency of use of energy substrates.