Dexamethasone effects on cerebral protein synthesis prior to and followinghypoxia-ischemia in immature rat

We hypothesized that the neuroprotection against cerebral hypoxic-ischemic damage observed with dexamethasone treatment in immature rats is related to a change in cerebral protein synthesis. Six-day-old Wistar rats were injec ted with either vehicle (10 ml/kg) or dexamethasone (0.1 mg/kg) 24 h prior to cerebral hypoxia-ischemia. Local cerebral protein synthesis (incorporati on of C-14-leucine into proteins) was measured in 7-day-old rats during nor moxia, during hypoxia-ischemia, and after hypoxia-ischemia which was produc ed with right carotid artery ligation and 2-h exposure to 8% O-2. In normox ic controls, cerebral protein synthesis was similar in dexamethasone and ve hicle-treated animals. During hypoxia-ischemia, local cerebral protein synt hesis decreased markedly (p < 0.0001) in ischemic regions ipsilateral to th e occlusion, irrespective of treatment. After hypoxia-ischemia, protein syn thesis declined even further in vehicle-treated animals. Reductions in prot ein synthesis were substantially more severe in vehicle- than dexamethasone -treated animals, particularly after hypoxia-ischemia (p < 0.0001). Thus, n europrotection with dexamethasone is not related to a reduction in basal le vels of cerebral protein synthesis, but is associated with an improved prot ein synthesis during and following hypoxia-ischemia. (C) 1999 Elsevier Scie nce inc.