PREVENTION OF HYPOXIC-ISCHEMIC DAMAGE WITH DEXAMETHASONE IS DEPENDENTON AGE AND NOT INFLUENCED BY FASTING

Pretreatment with the synthetic glucocorticoid dexamethasone prevents hypoxic-ischemic brain damage in 7-day-old neonatal rats. We presently characterize the response further by examining the effect of varying the age, the glucocorticoid, and the time of injection and by examinin g whether fasting can influence the response. Rats (n = 193) were rand omized to one of 16 different treatment groups and subjected to hypoxi a-ischemia (right carotid artery occlusion + 8% O-2 which was 3 h in d uration for 7-day 1 h for a-week, and 30 min for I-month-old animals). The brains were subsequently perfusion fixed and the area of infarcti on was measured from hematoxylin- and eosin-stained sections, Time dep endence studies demonstrated that treatment with 0.1 mg/kg intraperito neal dexamethasone 4 h prior to hypoxia reduced infarct size compared to vehicle-treated animals whereas pretreatment at either 48 h or 4 da ys was ineffective. Dexamethasone pretreatment (4 h) also provided neu roprotection against 4 h of hypoxia-ischemia. Fasted animals which rec eived dexamethasone had reduced blood glucose levels yet markedly less damage than controls, Another glucocorticoid, methylprednisolone (0.7 mg/kg), also reduced infarction, In 2-week-old animals the area of in farction was reduced by pretreatment with dexamethasone, whereas in 1- month-old animals dexamethasone was ineffective, The results suggest t hat a glucocorticoid-mediated response intervenes in events leading to neuronal death in young animals but not older animals once myelinatio n and synaptogenesis are complete. (C) 1995 Academic Press, Inc.