Unlike adults,
hyperglycemia with circulating
glucose concentrations of 25-35 mM/L protects the immature brain from hypoxic-ischemic damage. To ascertain the effect of
hyperglycemia on cerebral oxidative metabolism during the course of
hypoxia-
ischemia, 7-day postnatal rats underwent unilateral common carotid artery
ligation followed by exposure to 8% O2 for 2 h at 37 degrees C. Experimental animals received 0.2 cc s.c. 50%
glucose at the onset of
hypoxia-
ischemia, and 0.15
cc 25%
glucose 1 h later to maintain
blood glucose concentrations at 20-25 mM/L for 2 h. Control rat pups received equivalent concentrations or volumes of either
mannitol or 1 N saline at the same intervals. The cerebral metabolic rate for
glucose (CMRglc) increased from 7.1 (control) to 20.2 mumol 100 g-1 min-1 in hyperglycemic rats during the first hour of
hypoxia-
ischemia, 79 and 35% greater than the rates for saline-and
mannitol-injected animals at the same interval, respectively (p < 0.01). Brain intracellular
glucose concentrations were 5.2 and 3.0 mM/kg in the hyperglycemic rat pups at 1 and 2 h of
hypoxia-
ischemia, respectively;
glucose levels were near negligible in
mannitol- and saline-treated animals at the same intervals. Brain intracellular
lactate concentrations averaged 13.4 and 23.3 mM/kg in hyperglycemic animals at 1 and 2 h of
hypoxia-
ischemia, respectively, more than twice the concentrations estimated for the saline- and
mannitol-treated littermates.
Phosphocreatine (PCr) and
ATP decreased in all three experimental groups, but were preserved to the greatest extent in hyperglycemic animals. Results indicate that anaerobic glycolytic flux is increased to a greater extent in hyperglycemic immature rats than in normoglycemic littermates subjected to
cerebral hypoxia-ischemia, and that the enhanced glycolysis leads to greater intracellular
lactate accumulation. Despite cerebral lactosis, energy reserves were better preserved in hyperglycemic animals than in saline-treated controls, thus accounting for the greater resistance of hyperglycemic animals to hypoxic-ischemic brain damage.