Dexamethasone effects on cerebral protein synthesis prior to and following hypoxia-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 injected with either vehicle (10 ml/kg) or dexamethasone (0.1 mg/kg) 24 h prior to cerebral hypoxia-ischemia. Local cerebral protein synthesis (incorporation of 14C-leucine into proteins) was measured in 7-day-old rats during normoxia, during hypoxia-ischemia, and after hypoxia-ischemia which was produced with right carotid artery ligation and 2-h exposure to 8% O2. In normoxic controls, cerebral protein synthesis was similar in dexamethasone and vehicle-treated animals. During hypoxia-ischemia, local cerebral protein synthesis decreased markedly (p < 0.0001) in ischemic regions ipsilateral to the occlusion, irrespective of treatment. After hypoxia-ischemia, protein synthesis declined even further in vehicle-treated animals. Reductions in protein synthesis were substantially more severe in vehicle- than dexamethasone-treated animals, particularly after hypoxia-ischemia (p < 0.0001). Thus, neuroprotection with dexamethasone is not related to a reduction in basal levels of cerebral protein synthesis, but is associated with an improved protein synthesis during and following hypoxia-ischemia.
Tuor
U I
UI
Biosystems, Institute for Biodiagnostics, National Research Council of Canada, Winnipeg, Manitoba. tuor@ibd.nrc.ca
Manley
J J
JJ
Fyfe
C
C
Bascaramurty
S
S
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D009419:Nerve Tissue Proteins; D003907:Dexamethasone