EARLY METABOLIC ALTERATIONS IN EDEMATOUS PERIHEMATOMAL BRAIN-REGIONS FOLLOWING EXPERIMENTAL INTRACEREBRAL HEMORRHAGE

Object. The authors previously demonstrated, in a large-animal intrace rebral hemorrhage (ICH) model, that markedly edematous (''translucent' ') white matter regions (> 10% increases in water contents) containing high levels of clot-derived plasma proteins rapidly develop adjacent to hematomas. The goal of the present study was to determine the conce ntrations of high-energy phosphate, carbohydrate substrate, and lactat e in these and other perihematomal white and gray matter regions durin g the early hours following experimental ICH. Methods. The authors inf used autologous blood (1.7 ml) into frontal lobe white matter in a phy siologically controlled model in pigs (weighing approximately 7 kg eac h) and froze their brains in situ at 1, 3, 5, or 8 hours postinfusion. Adenosine triphosphate (ATP), phosphocreatine (PCr), glycogen, glucos e, lactate, and water contents were then measured in white and gray ma tter located ipsi-and contralateral to the hematomas, and metabolite c oncentrations in edematous brain regions were corrected for dilution. In markedly edematous white matter, glycogen and glucose concentration s increased two-to fivefold compared with control during 8 hours posti nfusion. Similarly, PCr levels increased several-fold by 5 hours, wher eas, except for a moderate decrease at 1 hour, ATP remained unchanged. Lactate was markedly increased (approximately 20 mu mol/g) at all tim es. in gyral gray matter overlying the hematoma, water contents and gl ycogen levels were significantly increased at 5 and 8 hours, whereas l actate levels were increased two-to fourfold at all times. Conclusions . These results, which demonstrate normal to increased high-energy pho sphate and carbohydrate substrate concentrations in edematous perihema tomal regions during the early hours following ICH, are qualitatively similar to findings in other brain injury models in which a reduction in metabolic rate develops. Because an energy deficit is not present: lactate accumulation in edematous white matter is not caused by stimul ated anaerobic glycolysis. Instead, because glutamate concentrations i n the blood entering the brain's extracellular space during ICH are se veral-fold higher than normal levels, the authors speculate, on the ba sis of work reported by Pellerin and Magistretti, that glutamate uptak e by astrocytes leads to enhanced aerobic glycolysis and lactate is ge nerated at a rate that exceeds utilization.