Correlation between glucose utilization and metabolite levels during focal ischemia in cat brain.

Abstract

MEASUREMENT of the cerebral rate of glucose consumption using radioactively labeled glucose 1 or glucose analogs 2 has potentially valuable clinical application.3 ' * These methods, however, do not distinguish between aerobic and anaerobic utilization of glucose. This distinction is particularly important for damaged brain in which the fraction of glucose metabolized anaerobically may be greater than normal. The presence of anaerobiosis can be detected by other methods, such as measurement of tissue levels of lactate. Thus, by combining a measure of tissue metabolite levels with a measure of glucose utilization, it is possible to make a qualitative distinction between aerobic and anaerobic metabolism.Marked regional variations in the rate of glucose consumption have been demonstrated in experimental models of cerebral ischemia 6 '" and hypoxia 7 using the f'4 C] deoxyglucose autoradiographic technique.1 Thus, occluding the middle cerebral artery in the cat resulted in closely juxtaposed regions of increased and decreased glucose utilization within the ischemic hemisphere. 6 Using the same model for the present study we have measured tissue levels of ATP, phosphocreatine, and lactate in regions with altered glucose consumption. By determining the uptake of [ 14 C] deoxyglucose in the same regional samples analyzed for metabolite content, it was possible to correlate variations in glucose utilization directly with anaerobic perturbations of metabolite levels. MethodsCats of either sex weighing between 3.5 and 4.0 kg were anesthetized with pentobarbital (40 mg/kg of body weight), immobilized with gallamine, and ventilated mechanically with 30% O a and 70% N 3 . Arterial blood gases were measured at predetermined intervals and arterial pressure was monitored continuously via femoral catheters. Arterial Pco a was maintained between 31 and 34 torr by adjusting respiratory rate and volume. Rectal temperature was held at 37°C with a servo-controlled heat lamp. The EEG was recorded from 2 pairs of brass electrodes which were screwed into the skull bilaterally over the ectosylvian gyri.The left middle cerebral artery was exposed via a transorbital approach. 8 The artery was occluded with a miniature Mayfield clip in 8 animals; 2 additional animals were sham-operated without occlusion. In 2 of the 8 experimental animals, arterial pressure was lowered to 90 torr by controlled hemorrhage in order to increase the degree of cerebral ischemia.At 60 At 90 min post-ischemia, the brain was frozen in situ by pouring liquid N, into a styrofoam cup placed over the intact calvarium. During 15 min of freezing, mechanical ventilation was continued and arterial pressure remained nearly normal. This technique freezes most regions of the brain without ischemic artifact 9 because deeper layers continue to be perfused until the arrival of the freezing front. The frozen brain was then sectioned in the coronal plane at 1 cm intervals with a pre-cooled saw, taking care to keep the tissue chilled with liquid N 2 .In a -30°C chamber, multiple sa...

Autoradiographic Determination of Cerebral Glucose Content, Blood Flow, and Glucose Utilization in Focal Ischemia of the Rat Brain: Influence of the Plasma Glucose Concentration

“…The cause of this increased glucose consumption found in normoglycemia, but not in hyperglycemia, has been a subject of controversy. It has been sug gested that anaerobic glycolysis can explain the phenomenon (Welsh et al, 1980). However, a cor relation has recently been reported between the in creased glucose utilization and sporadic transient increases in extracellular potassium in the cortical low-perfusion area (Nedergaard and Astrup, 1986).…”

Cerebral Blood Flow and Glucose Metabolism of the Ischemic Rim in Spontaneously Hypertensive Stroke-Prone Rats with Occlusion of the Middle Cerebral Artery

“…As a result, LCGU in the ischemic rim showed a pro nounced increase. A high LCGU in the border areas surrounding the acute focal ischemia was pre vi- ously noted by other investigators (Ginsberg et al, 1977 ;Welsh et al, 1980;Choki et aI., 1983;Sako et al, 1985). One explanation involves the excitatory hypothesis of neuronal cell death (Shiraishi et aI.…”

“…Previous studies of local cerebral glu cose utilization (LCGU) in the acute phase of focal ischemia in normotensive animals showed an in crease in LCG U in the border zone of the infarct (Ginsberg et aL, 1977;Welsh et aL, 1980;Choki et aL, 1983;Sako et aL, 1985). Spontaneously hyper-of 38% in the zone bordering the ischemic area.…”

“…LCGC showed little regional variation, but there was an increase Cerebral metabolism following acute focal isch emia has been studied in zones comprising the isch emic core. Previous studies of local cerebral glu cose utilization (LCGU) in the acute phase of focal ischemia in normotensive animals showed an in crease in LCG U in the border zone of the infarct (Ginsberg et aL, 1977;Welsh et aL, 1980;Choki et aL, 1983;Sako et aL, 1985). Spontaneously hyperReceived March 25, 1993; final revision received March 11, 1994; accepted June 28, 1994.…”

Cerebral blood flow, glucose utilization, and electrocorticograms following common carotid artery occlusion in gerbils.

“…There is indirect evidence that the narrow band at the periphery of the ischemic zone is caused by the activation of anaerobic glycolysis; in brain regions with increased 2-DG uptake, tissue levels of high-energy phosphates are reduced but not depleted while lactate accumulates, 3 and a narrow, well-defined boundary of increased glycogen phosphorylase activity is found around an ischemic core. 5 Because of the heterogeneity of 2-DG uptake, however, it is readily appreciated that such a tissue sampling method gives only a rough estimate of LCGU.…”