Kr. Wagner et al., EARLY METABOLIC ALTERATIONS IN EDEMATOUS PERIHEMATOMAL BRAIN-REGIONS FOLLOWING EXPERIMENTAL INTRACEREBRAL HEMORRHAGE, Journal of neurosurgery, 88(6), 1998, pp. 1058-1065
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.