Effect of glucose on recovery of energy metabolism following hypoxia-oligemia in mouse brain: dose-dependence and carbohydrate specificity.
Unilateral cerebral hypoxia-oligemia was produced in anesthetized mice using carotid artery occlusion combined with systemic hypoxia (10% O2). In the cerebral cortex ipsilateral to the carotid occlusion, ATP levels were depleted during a 30-min insult, but were restored to 64% of control during 60 min of recovery. Pretreatment of animals with glucose diminished the restoration of ATP in a dose-dependent manner. Thus, when blood glucose levels exceeded 12-13 mM (225 mg/dl), ATP recovery was greatly impaired. Neither galactose nor 3-O-methylglucose mimicked the detrimental effect of glucose. However, pretreatment with mannose, which is readily metabolized by brain, impaired restoration of ATP. The impairment, therefore, appears to be specific for substrates of cerebral metabolism. The ischemic accumulation of lactate in the ipsilateral cortex was augmented by only 30% at blood glucose levels well above the threshold for ATP recovery. Thus, unless recovery of energy metabolism is sensitive to small increments in brain lactate, it is difficult to explain the glucose-induced energy failure on the basis of enhanced lactic acidosis. Ipsilateral cerebral blood flow (CBF), measured with [14C]iodoantipyrine during hypoxia and recovery, was lower in glucose-pretreated than in saline-pretreated animals. However, the poor correlation between CBF and ATP, measured in the same tissue samples at 15 min recovery, failed to substantiate that regeneration of ATP was flow-limited early in recovery.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002241:Carbohydrates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D001786:Blood Glucose; D002241:Carbohydrates; D007773:Lactates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005947:Glucose