Dexamethasone prevents hypoxia/ischemia-induced reductions in cerebral glucose utilization and high-energy phosphate metabolites in immature brain.
We examined the potential importance of dexamethasone-mediated alterations in energy metabolism in providing protection against hypoxic-ischemic brain damage in immature rats. Seven-day-old rats (n = 165) that had been treated with dexamethasone (0.1 mg/kg, i.p.) or vehicle were assigned to control or hypoxic-ischemic groups (unilateral carotid artery occlusion plus 2-3 h of 8% oxygen at normothermia). The systemic availability of alternate fuels such as beta-hydroxybutyrate, lactate, pyruvate, and free fatty acids was not altered by dexamethasone treatment, and, except for glucose, brain levels were also unaffected. At the end of hypoxia, levels of cerebral high-energy phosphates (ATP and phosphocreatine) were decreased in vehicle- but relatively preserved in dexamethasone-treated animals. The local cerebral metabolic rate of glucose utilization (lCMRgl) was decreased modestly under control conditions in dexamethasone-treated animals, whereas cerebral energy use measured in a model of decapitation ischemia did not differ significantly between groups. The lCMRgl increased markedly during hypoxia-ischemia (p < 0.05) and remained elevated throughout ischemia in dexamethasone- but not vehicle-treated groups, indicating an enhanced glycolytic flux with dexamethasone treatment. Thus, dexamethasone likely provides protection against hypoxic-ischemic damage in immature rats by preserving cerebral ATP secondary to a maintenance of glycolytic flux.
Tuor
U I
UI
Biosystems, Institute for Biodiagnostics, National Research Council of Canada, Winnipeg, Manitoba.
Yager
J Y
JY
Bascaramurty
S
S
Del Bigio
M R
MR
D020155:3-Hydroxybutyric Acid; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries; D002560:Cerebrovascular Circulation; D003907:Dexamethasone / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D007839:Functional Laterality; D005947:Glucose / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D007773:Lactates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D006885:Hydroxybutyrates; D007773:Lactates; D011773:Pyruvates; D010725:Phosphocreatine; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D005947:Glucose; D020155:3-Hydroxybutyric Acid