Measurement of Free Glucose Turnover in Brain

Development of noninvasive techniques to discover new biomarkers in the live brain is important to further understand the underlying metabolic pathways of significance for processes such as anesthesia-induced apoptosis and cognitive dysfunction observed in the undeveloped brain. We used in vivo proton magnetic resonance spectroscopy and two different signal processing approaches to test the hypothesis that volatile (isoflurane) and intravenous (propofol) anesthetics at equipotent doses produce distinct metabolomic profiles in the hippocampus and parietal cortex of the live rodent. For both brain regions, prolonged isoflurane anesthesia was characterized by higher levels of lactate (Lac) and glutamate compared with long-lasting propofol. In contrast, propofol anesthesia was characterized by very low concentrations of Lac ([lac]) as well as glucose. Quantitative analysis revealed that the [lac] was fivefold higher with isoflurane compared with propofol anesthesia and independent of [lac] in blood. The metabolomic profiling further demonstrated that for both brain regions, Lac was the most important metabolite for the observed differences, suggesting activation of distinct metabolic pathways that may impact mechanisms of action, background cellular functions, and possible agent-specific neurotoxicity.

Section: Discussionmentioning

confidence: 99%

The metabolomic profile during isoflurane anesthesia differs from propofol anesthesia in the live rodent brain

Makaryus

Lee

et al. 2011

“…For the calculation of LCMRglc, the operational equa tion of Sokoloff et al (1977) as modified for changing plasma glucose level by Savaki et al (1980) was used. The equation that allows for changes in glucose level was used since in some animals the glucose level changed slowly «0.5%/min) throughout the LCMRglc measurement.…”

Section: Methodsmentioning

confidence: 99%

Local Cerebral Glucose Utilization in Chronic Middle Cerebral Artery Occlusion in the Cat

Komatsumoto

Greenberg²,

Hickey

et al. 1989

Summary: This study examines the correlation between local CMRglc (LCMRglc) alterations and clinicopatholog ical changes in a chronic middle cerebral artery (MCA) occlusion model in the cat. The left MCA was occluded for a period of 2 h. The animals were grouped into mild, moderate, and severe ischemia based on the depression of the EEG 30 min after the MCA occlusion. Follow ing release of the clip, the animals were allowed to re cover for a week during which time daily neurological examinations were performed. On the seventh day P4C]2-deoxyglucose was injected for the determination of LCMRglc• Alternative blocks were processed for histo logical evaluation in which both neuronal and phagocytic changes were graded into four categories (0 = normal to 3 = severe). LCMRglc (J.LmollIOO glmin) in the ischemic hemisphere (all histological grades) was significantly lower than the metabolic rate in comparable regions of the sham MCA occlusion group. Regions with significant phagocytosis (grade 2 and 3) invariably exhibited acti vated glucose metabolism (57.4 ± 8.4 and 105.9 ± 6.8 J.Lmol/lOO glmin, respectively), which was significantlyThe recovery process of brain tissue after an isch emic insult may be closely related to its metabolic state. Although the recent development of positron emission tomography has offered the potential for investigating glucose metabolism of the human brain Phelps et al., 1982), few studies have been made early following a stroke (Kuhl et al., 1980;Lenzi et al., 1982;Wise et al., 1983;Baron et al., 1984;Kushner et al., 1987). These findings provided some information about Abbreviations used: 2-DG, 2-deoxyglucose; LC, lumped con stant; LCMRgl c, local CMRglc; MCA, middle cerebral artery. 535higher than in regions without phagocytosis (30.4 ± 0.8 J.LmolllOO g/min). There was a significant gradient of me tabolism in the central, peripheral, and boundary zone and the non-MCA territory in the animals with severe ischemic lesions. LCMRglc in the central MCA territory was well correlated with the EEG amplitude changes (r = 0.82, p < 0.05) and the morphological score (r = -0.89, p < 0.05). The metabolic rate was significantly depressed in both the ipsilateral and the contralateral central MCA territories in comparison with the sham occlusion ani mals. The depression in LCMRglc in the contralateral hemisphere correlated well with the concomitant depres sion in the contralateral EEG amplitude. These studies demonstrate that local heterogeneous metabolic alter ations and contralateral cortical diaschisis exist chroni cally following temporary MCA occlusion and that the increases in local cerebral glucose metabolism seen in chronic stroke may be due to phagocytotic activity.

“…For the calculation of LCMRgl, the operational equation of Sokoloff et al (1977) as mod ified for changing plasma glucose level by Savaki et al (1980) was used. The lumped constant for normal anes thetized cats (0.411) (Sokoloff, 1981a) was used, since there is no evidence of a significant difference in the lumped constant between normal brain and postischemic reperfused brain (Ginsberg and Reivich, 1979).…”

Section: Methodsmentioning

confidence: 99%

Regional Flow-Metabolism Couple following Middle Cerebral Artery Occlusion in Cats

Tanaka¹,

Greenberg²,

Gonatas

et al. 1985

Summary:The regional flow-metabolism couple was studied during the recovery period after I h of left middle cerebral artery (MCA) occlusion in cats. Local CBF (LCBF) was assessed at the end of ischemia as well as at the end of 4 h of recirculation by the microsphere tech nique. Local CMRgl (LCMRgl) was measured at the end of the recirculation period with [14C12-deoxyglucose. His tology was evaluated by light microscopy from coronal brain blocks adjacent to those used for the determination of LCBF and LCMRgl. When LCBF in the central and peripheral MCA territories during the recovery period was between 40 and 115% of the value in sham occlusion studies, LCMRgl was greater than the control level found in the sham studies, and was accompanied by slight his tological damage. This finding suggests that anaerobic glycolysis may persist after transient ischemia in spite of