The effect of hyperglycemia on cerebral metabolism during hypoxia-ischemia in the immature rat.
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.
Vannucci
R C
RC
Department of Pediatrics (Pediatric Neurology), Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center 17033-0850, USA.
Brucklacher
R M
RM
Vannucci
S J
SJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002339:Carotid Arteries / Q000601:surgery; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D006019:Glycolysis; D006943:Hyperglycemia / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008026:Ligation; D010100:Oxygen / Q000008:administration & dosage; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007773:Lactates; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D010100:Oxygen