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.