Skip to main content
Intended for healthcare professionals
Free access
Research article
First published June 2003

Lactate: A Preferred Fuel for Human Brain Metabolism in Vivo

Diarmuid Smith, Andrew Pernet, William A. Hallett, Emma Bingham, Paul K. Marsden, and Stephanie A. Amiel [email protected]View all authors and affiliations
Volume 23, Issue 6
https://doi.org/10.1097/01.WCB.0000063991.19746.11

Abstract

Recent in vitro studies suggest that lactate, rather than glucose, may be the preferred fuel for neuronal metabolism. The authors examined the effect of lactate on global brain glucose uptake in euglycemic human subjects using 18fluorodeoxyglucose (FDG) positron emission tomography (PET). Eight healthy men, aged 40 to 54 years, underwent a 60-minute FDG-PET scan on two occasions in random order. On one occasion, 6.72% sodium lactate was infused at a rate of 50 μmol · kg−1 · min−1 for 20 minutes and then reduced to 30 μmol · kg−1 · min−1; 1.4% sodium bicarbonate was infused as a control on the other occasion. Plasma glucose levels were not different between the two groups (5.3 ± 0.23 and 5.3 ± 0.24 mmol/L, P = 0.55). Plasma lactate was significantly elevated by lactate infusion (4.08 ± 0.35 vs. 0.63 ± 0.22 mmol/L, P < 0.0005. The whole-brain rate of glucose uptake was significantly reduced by approximately 17% during lactate infusion (0.195 ± 0.022 vs. 0.234 ± 0.020 μmol · g−1 · min−1, P = 0.001). The authors conclude that, in vivo in humans, circulating lactate is used by the brain at euglycemia, with sparing of glucose.
Glucose has traditionally been considered the only substrate capable of satisfying the brain's energy requirement (Siesjo, 1978). There is, however, mounting evidence from in vitro experiments that lactate, a nonglucose fuel, is an efficient energy substrate for neurons and may be used preferentially by neurons to maintain synaptic transmission, particularly during periods of intense activity. For example, neurons bathed in a medium containing 5-mmol/L glucose and 5- to 10-mmol/L lactate generate significantly more cellular energy from lactate than glucose (Larrabee et al., 1995; Taberno et al., 1978). Lactate alone can support synaptic function in rat hippocampal slices (Schurr et al., 1988; Stittsworth and Lanthorn, 1993) and is the preferred energy substrate for recovery of neuronal function after prolonged oxygen deprivation (Schurr et al., 1997).
Lactate is produced locally within the brain by astrocytes, in an activity-dependent glutamate-mediated manner (Pellerin and Magistretti, 1994). The excitatory neurotransmitter glutamate stimulates glycolysis within the astrocyte to generate and release lactate, which is then taken up by neurons as an aerobic energy substrate that enables neurons to endure activation. Blood-borne lactate was not thought to be a significant source of brain lactate as there was early evidence that it does not cross the blood–brain barrier easily (Pardridge and Oldendorf, 1977). However, mammalian brain does contain transport mechanisms that allow lactate to cross the blood–brain barrier via specialized monocarboxylate transporters (MCT) (Dringen et al., 1995; Price et al., 1998; Tildon et al., 1993). The efficiency of passage of lactate across the blood–brain barrier has been estimated to be between 25% and 50% that of glucose (Cremer et al., 1979; Knudsen et al., 1991). Although there are few data in vivo in humans, clinical studies do support the hypothesis that, when glucose is in short supply, circulating lactate can support cortical and other brain functions. Elevated circulating lactate levels reduce the symptoms, cognitive impairment and counterregulatory hormone responses to acute hypoglycemia, whether created endogenously by strenuous exercise (Coyle et al., 1986; Felig et al., 1982) or by infusion of exogenous lactate (King et al., 1997; Maran et al., 1994; Veneman et al., 1994). However, there are no human in vivo data examining the brain's ability to use lactate outside the setting of glucose deprivation.
Global and regional brain glucose metabolism can be examined in vivo in humans using neuroimaging techniques, such as [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET). FDG is an analog of natural glucose (deoxyglucose) labeled with a positron emitter (18F). Deoxyglucose is taken up by the cells and phosphorylated, but then proceeds no further along the intracellular glucose metabolic pathway. Accumulation of labeled deoxyglucose in tissue cells has long been used as a way of measuring glucose uptake and initial metabolism in many tissues, including the brain in human subjects in vivo (Phelps et al., 1979). To investigate the hypothesis that healthy human brain will use lactate in preference to glucose even when glucose is readily available, we measured global and regional brain glucose uptake using FDG PET in healthy human volunteers at normal fasting plasma glucose levels.

MATERIALS AND METHODS

Research design

Eight healthy male volunteers aged 40 to 54 years (mean ± SD age, 45.0 ± 5.48 years) were studied. None was taking any medication or had a history of cardiovascular disease or a personal and family history of diabetes mellitus. The protocol was approved by the ethics committee of Guy's and St. Thomas' Hospital trust and ARSAC (Administration of Radioactive Substances Advisory Committee) and conducted in accordance with the principles of the Helsinki declaration. All subjects gave written informed consent before participating. Each subject was studied twice (2–8 weeks apart) with an FDG-PET scan to measure global and regional brain glucose uptake. Magnetic resonance imaging (MRI) scans for anatomic detail were performed once in each subject on a separate occasion and were coregistered with the PET images.

Study protocol

Positron emission tomography was performed at the Clinical PET Center, St. Thomas' Hospital (London, U.K.) using an ECAT 951R PET scanner (CTI/Siemens, Knoxville, TN, U.S.A.). The scanner has an axial field of view of 10.8 cm and an intrinsic in-plane spatial resolution of 6.2 mm transaxially and 4.5 mm axially.
Subjects were admitted to the PET Center before 9 a.m. They had avoided alcohol for the previous day and had fasted from 10:30 p.m. the previous evening. An intravenous catheter was inserted in a large vein in the antecubital fossa of the dominant arm, using full aseptic techniques and local anesthetic (intradermal 1% lidocaine) for infusion of lactate or sodium bicarbonate. After ensuring the patency of a collateral circulation, a second catheter was inserted in the radial artery of the nondominant hand, again aseptically and with local anesthetic. This catheter was used for rapid arterial sampling during the study.
At time = 0 minutes, an intravenous infusion of either a 0.6-mmol/mL sodium lactate (diluted and sterilized in the hospital pharmacy and tested for pyrogens before infusion) or sodium bicarbonate was started. The lactate was infused via a sterile μm filter at a rate of 50 μmol · kg−1 · min−1 via a 20-μm filter for 20 minutes, and was reduced thereafter to a rate of 30 μmol · kg−1 · min−1 for the remainder of the study.
In the control study, sodium bicarbonate was infused instead of sodium lactate, to mimic the pH changes in the blood induced by sodium lactate. The first three subjects were infused with 1.24% sodium bicarbonate (Polyfusor; Fresenius, Warrington, U.K.), whereas the remaining 5 received 1.4% sodium bicarbonate (Polyfusor; Fresenius). The dose of the bicarbonate was calculated as 0.25 times the lactate dose in mmol/h. Studies were done in random order and subjects were blinded to the nature of the infusion.
Arterial blood samples for plasma glucose and lactate were taken every 5 minutes and analyzed at the bedside (Yellow Springs 2300 STAT Plus glucose analyzer; Yellow Springs Instruments, Yellow Springs, OH, U.S.A.). Arterial samples for pH were collected in a 2-mL heparinized syringe at 30-minute intervals, placed on ice, and immediately measured in an arterial blood gas machine (AVL Omni 9; Roche Diagnostics, Graz, Austria).
With the lactate–bicarbonate infusion running, the volunteer was positioned comfortably in the PET scanner with his head movement restrained by a headband. Head position within the scanner was aligned axially to the orbitomeatal line and checked periodically by means of two laser beams on the camera gantry. Sensory disturbance was standardized by studying subjects with their eyes shut and in the background scanner noise. A 10-minute transmission scan was made to correct for photon attenuation. At time = 40 minutes, approximately 125 MBq FDG was injected intravenously over 20 seconds. Dynamic scanning of 23 frames of variable duration was begun 10 seconds before the injection of tracer and continued for the following 60 minutes. Continuous online sampling to detect 18FDG tracer levels in arterial blood was started 1 minute before tracer injection and continued for 30 minutes, with arterial blood drawn at 5 mL/min for 15 minutes, then 2 mL/min for 15 minutes (IVAC572 peristaltic pump; Lily Industries, San Diego, CA, U.S.A.) through a Bismuth Germinate Oxalate Crystal Fluid Analyzer (Allogg, Stockholm, Sweden). Timed 2-mL hand-drawn arterial blood samples were taken at 5-minute intervals throughout the period of the scan. One milliliter was used for measurement of plasma glucose and lactate, and the other milliliter was used to measure the plasma tracer radioactivity concentration in a well counter. The well-counter measurements were used to calibrate the online fluid analyzer data appropriately for subsequent analysis.
At the end of the 18FDG scan, the infusion was stopped and both arterial and intravenous lines removed. Before conducting second scans, the previous arterial cannulation site was examined and the hand was reexamined for collateral circulation.
On separate occasions, each subject also underwent a standard magnetic resonance imaging brain scan for anatomic detail for later coregistration with the PET images to obtain data from brain regions of interest.

Data analyses

All images were reconstructed by filtered back-projection and smoothed with a Hanning filter, such that the spatial resolution was 8.5-mm full-width at half maximum both transaxially and axially. Reconstructed images were displayed in a matrix of 128 × 128 × 31-voxel format, each voxel measuring 2.0 × 2.0 × 3.43 mm. FDG uptake images were formed by summation of images acquired between 30 and 60 minutes postinjection.

Whole-brain rate of glucose uptake with and without lactate

For each PET study, the dynamic PET image data and the arterial input function were combined to produce a parametric image of the rate of glucose utilization using the generic method described by Patlak et al. (1983). This method requires that concentrations of unbound FDG in plasma and tissue rapidly reach equilibrium, and that phosphorylated FDG remains trapped in tissue for the duration of the study. The work of Phelps et al. (1979) has shown that these assumptions are valid for FDG in the brain. This procedure provides a measure of the rate of glucose utilization that is independent of changes in the arterial tracer and glucose concentration between subjects and between studies. To provide a quantitative value for the rate of glucose uptake it is necessary to apply a “lumped constant” (LC), which accounts for the difference in behavior between FDG and native glucose. We used the value of 0.52 for LC (Reivich et al., 1985) because this has been commonly used in the literature. More recent measurements suggest that the true value of LC at normoglycemia is probably in the range 0.8 to 0.9 (Hasselbalch et al., 2001, Graham et al., 2002), and we also give the global rates of glucose utilization calculated with a LC of 0.8. The value chosen for LC is applied as a simple scaling factor and does not affect the statistical significance of our results. The average whole-brain rate of glucose uptake was calculated for the two different conditions (i.e., with lactate or with bicarbonate) by addition of all brain image slices after application of a 40% threshold to exclude noncerebral tissue activity.
Regional brain FDG uptake. To examine for regional differences in the FDG uptake images between the two groups over and above any whole-brain changes identified using the quantitative analysis, statistical parametric mapping (SPM) was performed using the SPM99 program (Wellcome Department of Cognitive Neurology, London; implemented in Matlab 6.0; MathWorks, Natick, MA, U.S.A.) (Reed et al., 1999).
The SPM analysis was performed on the 30- to 60-minute summed uptake images, which have superior signal-to-noise properties to the quantitative Patlak images. Each subject's scan was transformed into standard stereotactic space using a 12-parameter linear transformation, followed by a nonlinear deformation using basis functions to allow for intersubject averaging and comparisons (Friston et al., 1995, 1996). Smoothing using a Gaussian kernel of 20 mm was performed to allow for intraindividual differences in gyral anatomy and to increase the signal-to-noise ratio. The effect of variation in whole-brain FDG uptake among different scans from differing injected activities, plasma glucose concentrations, and plasma FDG concentrations was removed by scaling voxel values to the mean whole-brain uptake.
Comparisons to determine the effect of lactate or bicarbonate infusion were made by definition of the appropriately weighted linear contrasts within SPM99, and SPM t maps of voxel-byvoxel t statistics were generated. In this exploratory analysis, clusters of voxels surviving an equivalent threshold Z score >3.09 (omnibus threshold P < 0.001), uncorrected for multiple comparisons, were considered to show significant differences (Friston et al., 1996). To enhance anatomic localization, the locations of volumes of change were displayed by rendering the maximum intensity map onto orthogonal planes of a high-resolution T1-weighted MRI brain scan in Talairach space provided with the SPM99 software (Studholme et al., 1997).
To investigate potential differential changes between gray and white matter in particular, a region of interest (ROI) analysis was also performed. Ten-millimeter-diameter ROIs were placed over cortical gray matter, the basal ganglia, and white matter on the MR scans and than transferred to coregistered PET images. The analysis was done on both the Patlak data and on the raw FDG uptake data, as the signal to noise ratio is greater with the latter.

Statistical analysis

Data are presented as mean ± SD unless otherwise stated. Metabolic data were compared between the lactate and bicarbonate groups by analysis of variance (ANOVA) with repeated measures design. Whole-brain FDG uptake data were compared using paired t tests. These analyses were carried out using SPSS for Windows 10.5 (SPSS, Chicago, IL, U.S.A.).

RESULTS

Biochemical changes

There was no difference in plasma glucose concentration at baseline or during the studies between lactate and bicarbonate (5.3 ± 0.23 vs. 5.2 ± 0.54, P = 0.62; 5.3 ± 0.24 vs. 5.2 ± 0.21 mmol/L, P = 0.55). The coefficient of variation of the plasma glucose during each study was 1.04% and 0.87% respectively (Fig. 1). As shown in Fig. 2, the plasma lactate concentration rose significantly, resulting in marked hyperlactemia during the lactate infusion compared with the bicarbonate study (0.62 ± 0.12 to 4.08 ± 0.35 vs. 0.85 ± 0.24 to 0.63 ± 0.22 mmol/L, P < 0.0005). pH values were not different between the two groups at baseline (7.39 ± 0.03 vs. 7.39 ± 0.01, P = 0.39) and increased significantly in both groups during infusion (7.39 ± 0.03 to 7.47 ± 0.03, P = 0.0007; 7.39 ± 0.01 to 7.42 ± 0.01, P = 0.0004). The rise in pH was greater in the lactate group, P = 0.004.
FIG. 1. Plasma glucose concentration during the lactate and bicarbonate infusions. Data are expressed as mean ± SE. Open circles, bicarbonate; Solid squares, lactate study.
FIG. 2. Plasma lactate concentrations during the lactate and bicarbonate infusions. The arrow represents the time of injection of the 18FDG tracer. Data are expressed as mean ± SE. The symbols are the same as those used in Fig. 1.

Whole-brain rate of glucose uptake

Whole-brain rate of glucose uptake was significantly lower in the lactate group with a 17% reduction in brain FDG uptake compared with the bicarbonate group (0.195 ± 0.02 and 0.234 ± 0.02 μmol · g−1 · min−1, P < 0.001). As shown in Fig. 3, all eight subjects showed a reduction in brain glucose uptake; this ranged between 11% and 30% in seven subjects, but was only 3% in the eighth subject. It should be noted that if a LC of 0.8 is used, the data for global CMRglu translate to 0.127 ± 0.014 and 0.152 ± 0.012 μmol · g−1 · min−1 (P < 0.001).
FIG. 3. Calculated cerebral glucose uptake (μmol · g−1 · min−1) in individual subjects. The bicarbonate infusion data are displayed on the left, while the lactate data can be found on the right.

Regional changes

Figure 4 shows the result of the SPM analysis. No significant regional differences between the lactate and bicarbonate studies were identified. With the display set as in the Figure (SPM height threshold t + 1.89), a large area in the center of the brain and excluding cortical gray matter is seen. This is consistent with there being a larger fall in CMRglu in gray matter than in the white matter during lactate infusion; however, the region does not reach significance.
FIG. 4. Statistical parametric maps indicating regional differences between the lactate and bicarbonate studies. All areas indicated are below the level of significance.
Regional CMRglu values obtained in the ROI analysis are shown in Table 1. Both gray and white matter regions showed lower values of CMRglu with lactate than with bicarbonate (cortical gray matter, 0.225 ± 0.030 vs. 0.273 ± 0.027 μmol · g−1 · min−1, P = 0.0013; basal ganglia, 0.221 ± 0.029 vs. 0.258 ± 0.030 μmol · g−1 · min−1, P = 0.021; white matter, 0.125 ± 0.023 vs. 0.158 ± 0.022 μmol · g−1 · min−1, P = 0.0045). The average differences (bicarbonate-lactate) observed in the ratio between gray and white matter were −5.1% (P = 0.44) for the Patlak data and 2.4% (P = 0.22) for the raw FDG uptake data, neither being significant.
TABLE 1. Regional CMRglu values in umol/g/min
  Whole brain Cortical gray matter White matter Basal ganglia
 
  L B L B L B L B
Subject 1 0.195 0.236 0.252 0.291 0.112 0.179 0.212 0.251
Subject 2 0.190 0.196 0.228 0.223 0.121 0.128 0.226 0.200
Subject 3 0.180 0.235 0.207 0.277 0.095 0.142 0.219 0.277
Subject 4 0.208 0.236 0.237 0.281 0.122 0.177 0.230 0.239
Subject 5 0.161 0.230 0.171 0.244 0.123 0.149 0.191 0.259
Subject 6 0.236 0.264 0.256 0.295 0.170 0.177 0.286 0.299
Subject 7 0.197 0.229 0.250 0.299 0.115 0.123 0.211 0.283
Subject 8 0.191 0.251 0.201 0.273 0.143 0.177 0.194 0.259
Mean 0.195 0.234 0.225 0.273 0.125 0.158 0.221 0.258
SD 0.022 0.020 0.030 0.027 0.023 0.022 0.030 0.030
LC = 0.52.
L, lactate; B, bicarbonate.

DISCUSSION

Lactate can cross the blood–brain barrier with a permeability about 50% that of glucose (Knudsen et al., 1991) and is capable of sustaining cerebral function during times of glucose deprivation (King et al., 1997, 1998; Maran et al., 1994; Veneman et al., 1994). However, its potential to act as an alternate or preferred fuel to glucose in sustaining neuronal function at normal blood glucose concentrations in humans is unknown. Using FDG-PET we have shown a 17% reduction in whole-brain rate of glucose uptake during a systemic infusion of lactate at euglycemia. This is compatible with the hypothesis that the human brain can access circulating lactate and then use it in preference to glucose as a metabolic fuel.
The global reduction in CMRglu in the presence of lactate could be related to generalized feedback inhibition secondary to increased availability of pyruvate for oxidation. The observation of a greater effect in gray matter would indicate a selective effect of lactate on neuronal metabolism; however, we cannot conclude this from our data. Owing to contamination of small white matter regions by gray matter, it is difficult to obtain reliable values for white matter alone, and so it may be that the increase in white matter that we observed is artefactual. It is interesting that a central region largely excluding gray matter was seen with the SPM map, but it was below the commonly accepted significance threshold for SPM. Our observations may still therefore be compatible with an increase in CMRglu for gray matter alone, but the quality of the data is not adequate to confirm this.
Recent in vitro evidence shows that, even when glucose is fully available, neurons use lactate in preference to glucose to sustain function, particularly during times of neuronal activation (Larrabee, 1995; Schurr et al., 1988, 1999). The astrocyte-neuron lactate shuttle hypothesis states that neural activity increases the extracellular concentration of the excitatory neurotransmitter glutamate, the uptake of which by brain astrocytes stimulates astrocyte Na+ − K+ ATPase, glucose uptake, and aerobic glycolysis, with consumption of glucose and production of lactate (Magistretti and Pellerin, 1997; Pellerin and Magistretti, 1997). The lactate then leaves the astrocyte and is taken up by neurons as an aerobic energy substrate (Schurr et al., 1999). In the neuron, the lactate enters the tricarboxylic acid cycle (TCA) via pyruvate, such that one lactate molecule entering the TCA cycle can yield 17 ATP molecules in the presence of normal oxygen and glucose (Magistretti and Pellerin, 1997). The conversion of lactate to pyruvate for entry into the TCA cycle is preferred thermodynamically over the conversion of glucose to pyruvate because the latter requires the investment of ATP, whereas the former does not (Magistretti and Pellerin, 1997). Exogenous lactate from the peripheral circulation, crossing the blood–brain barrier, would provide lactate directly for entry into the neuron to serve as the primary fuel for neural activity. Such a mechanism would explain our data.
Traditionally it has been thought that systemic lactate could not act as an energy substrate for neurons (Pardridge and Oldendorf, 1977). The blood–brain barrier contains the messenger RNA for the MCTs necessary for the transport of lactate across cellular membranes (Hanu et al., 2000; Price et al., 1998) and is permeable to lactate (Knudsen et al., 1991). The ability of elevated circulating lactate to reduce the symptoms, cognitive dysfunction, and centrally mediated counterregulatory hormone responses to acute hypoglycemia, when elevated either by exercise (Coyle et al., 1986; Felig et al., 1982) or by infusion (King et al., 1998; Maran et al., 1994; Veneman et al., 1994) in human studies, attests to the ability of the lactate to cross the blood–brain barrier in humans and replace glucose as a neuronal metabolic fuel when glucose supplies from the circulation are reduced. However, the present study is the first to show a reduction in brain glucose metabolism during normal glucose availability in humans. In our study, lactate concentrations rose to a similar degree observed during moderate exercise (Hirsch et al., 1989; Stanley et al., 1985) and in the acute hypoglycemia studies of Veneman et al. (1994) and King et al. (1998).
Might there be another explanation for the reduction in rate of glucose uptake observed in our lactate-infusion study? We used sodium bicarbonate as a control to mimic the changes in acid–base balance induced by lactate infusion. Although we achieved a significant rise in pH during both studies, the rise was greater in the lactate group. There are data to show that extracellular acidification increases lactate uptake into cells both in vitro (Lomneth et al., 1990; McKenna et al., 1998; Walz and Mukerji 1990) and in vivo (Knudsen et al., 1991). Therefore, the raised pH of our study may have inhibited cell lactate uptake, reducing the observable effect on glucose metabolism. In other words, the change in pH could have only reduced the magnitude of the effect observed. Might changes in cerebral blood flow account for the reduction in rate of glucose uptake? Infusion of hypertonic sodium lactate in a porcine model of focal cryogenic brain injury increased cerebral blood flow and oxygen delivery compared with placebo (Shackford et al., 1992). Cerebral blood flow was not measured in this study; however, an increase in cerebral blood flow alone (i.e., without an accompanying increase in the rate of glucose uptake) would not explain the observed change in rate of glucose uptake. Owing to the low permeability surface area product for glucose and FDG, the rate of glucose uptake as determined by PET is very insensitive to changes in blood flow (Huang and Phelps, 1986).
Although different isoforms of MCT transporters and the enzyme lactate dehydrogenase may predominate in different brain cells and regions, both are found in astrocytes and neurons throughout the brain, supporting the concepts of the lactate shuttle and the use of lactate by the whole brain. MCT2, found in tissues that take up rather than release lactate (Pellerin et al., 1998; Pierre et al., 2002), and LDH5, which preferentially catalyzes the conversion of lactate to pyruvate (Bittar et al., 1996), are both characteristic of neurons.
In conclusion, our data support the hypothesis that the human brain uses circulating lactate, at least to some extent in preference to glucose to sustain metabolism at normal blood glucose concentrations. This finding helps us understand more about human brain glucose metabolism and illustrates the potential therapeutic benefits of lactate in protecting and sustaining normal brain function.

Acknowledgments:

The authors thank Paul Forsey (Pharmacy Department, St. Thomas' Hospital) for preparing the sodium lactate used in these experiments, and the staff of the St Thomas Clinical PET Center for their invaluable support in running these studies.

REFERENCES

Bittar PG, Charnay Y, Pellerin L, Bouras C, Magistretti PJ (1996) Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. J Cereb Blood Flow Metab 16:1079–1089
Crossref
PubMed
ISI
Google Scholar
Coyle E, Coggan A, Hemmert M, Ivy J (1986) Muscle glycogen utilization during prolonged strenuous exercise when fed carbohydrate. J Appl Physiol 61:165–172
Crossref
PubMed
ISI
Google Scholar
Cremer JE, Cunningham VJ, Pardridge WM, Braun LD, Oldendorf WH (1979) Kinetics of blood brain barrier transport of pyruvate, lactate and glucose in suckling, weaning and adult rats. J Neurochem 33:439–445
Crossref
PubMed
ISI
Google Scholar
Dringen R, Peters H, Wiesinger H, Hamprecht B (1995) Lactate transport in cultured glial cells. Dev Neurosci 17:63–69
Crossref
PubMed
ISI
Google Scholar
Felig P, Cherif A, Minegawa A, Wahren J (1982) Hypoglycaemia during prolonged exercise in normal man. N Engl J Med 306:895–900
Crossref
PubMed
ISI
Google Scholar
Friston KJ, Holmes AP, Worsley KJ, Poline J-B, Frith CD, Frackowiak RSJ (1995) Spatial registration and normalisation of images. Human Brain Mapping 2:189–210
Crossref
Google Scholar
Friston KJ, Holmes A, Poline J.-B, Frith CD (1996) Detecting activations in PET and fMRI: levels of interference and power. Neuoroimage 40:223–235
Crossref
ISI
Google Scholar
Graham MM, Muzi M, Spence AM, O'Sullivan F, Lewellen TK, Link JM, Krohn KA (2002) The FDG lumped constant in normal human brain. J Nuc Med 43:1157–1166
PubMed
ISI
Google Scholar
Hanu R, McKenna M, O'Neill A, Resneck WG, Bloch RJ (2000) Monocarboxylate acid transporters, MCT1 and MCT2, in cortical astrocytes in vitro and in vivo. Am J Physiol 278: C921–C930
Crossref
Google Scholar
Hasselbalch SG, Holm S, Pedersen HS, Svarer C, Knudsen GM, Madsen PL, Paulson OB (2001) The F-18-fluorodeoxyglucose lumped constant determined in human brain from extraction fractions of F-18-fluorodeoxyglucose and glucose. J Cereb Blood Flow Metab 21:995–1002
Crossref
PubMed
ISI
Google Scholar
Hirsch I, Marker J, Smith L, Spina R, Parvin C, Hollszy J, Cryer P (1989) Insulin and glucagon in prevention of hypoglycaemia during exercise in humans. Am J Physiol 256:E695–E704
Google Scholar
Huang SC, Phelps ME (1986) Principles of tracer kinetic modeling in positron emission tomography and autoradiography. In: Positron emission tomography and autoradiography: principles and applications for the brain and heart (Phelps ME, Mazziotta JC, Schelbert HR eds), New York: Raven Press, pp 287–346
Google Scholar
King P, Kong MF, Parkin H, Macdonald IA, Barber C, Tattersall RB (1998) Intravenous lactate prevents cerebral dysfunction during hypoglycaemia in insulin-dependent diabetes mellitus. Clin Sci 94:157–163
Crossref
PubMed
ISI
Google Scholar
King P, Parkin H, Macdonald IA, Barber C, Tattersall RB (1997) The effect of intravenous lactate on cerebral function during hypoglycaemia. Diabet Med 14:19–28
Crossref
PubMed
ISI
Google Scholar
Knudsen GM, Paulson OB, Hertz MM (1991) Kinetics of blood brain barrier transport of lactate and its influence by hypercapnia. J Cereb Blood Flow Metab 11:581–586
Crossref
PubMed
ISI
Google Scholar
Larrabee MG (1995) Lactate metabolism and its effects on glucose metabolism in an excised neural tissue. J Neurochem 64:1734–1741
Crossref
PubMed
ISI
Google Scholar
Lomneth R, Medrano S, Gruenstein EL. (1990) The role of transmembrane pH gradients in the lactic acid induced swelling of astrocytes. Brain Res 523:69–77
Crossref
PubMed
ISI
Google Scholar
Magistretti PJ, Pellerin L (1997) Metabolic coupling during activation: a cellular view. Adv Exp Med Biol 413:161–166
Crossref
PubMed
ISI
Google Scholar
Maran A, Cranston I, Lomas J, Macdonald I, Amiel SA (1994) Protection by lactate of cerebral function during hypoglycaemia. Lancet 343:16–20
Crossref
PubMed
ISI
Google Scholar
McKenna MC, Tildon JT, Stevenson JH, Hopkins IB, Huang X, Couto R (1998) Lactate transport by cortical synaptosomes from adult rat brain: characterization of kinetics and inhibitor specificity. Dev Neurosci 20:300–309
Crossref
PubMed
ISI
Google Scholar
Pardridge WM, Oldendorf WH (1977) Transport of metabolic substrates through the blood-brain barrier. J Neurochem 28:5–12
Crossref
PubMed
ISI
Google Scholar
Patlak CS, Blasberg RG, Fenstermacher JD (1983) Graphical evaluation of blood to brain transfer constants from multiple time uptake data. J Cereb Blood Flow Metab 3:1–7
Crossref
PubMed
ISI
Google Scholar
Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 91:10625–10629
Crossref
PubMed
ISI
Google Scholar
Pellerin L, Magistretti PJ (1997) Glutamate uptake stimulates Na+/K+ ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain. J Neurochem 69:2132–2137
Crossref
PubMed
ISI
Google Scholar
Pellerin L, Pellegri G, Martin JL, Magistretti PJ (1998) Expression of monocarboxylate transporter mRNAs in mouse brain: support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain. Proc Natl Acad Sci U S A 95:3990–3995
Crossref
PubMed
ISI
Google Scholar
Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)-2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 6:371–388
Crossref
PubMed
ISI
Google Scholar
Pierre K, Magistretti PJ, Pellerin L (2002) MCT2 is a major neuronal monocarboxylate transporter in the adult mouse brain. J Cereb Blood Flow Metab 22:586–595
Crossref
PubMed
ISI
Google Scholar
Price NT, Jackson VN, Halestrap AP (1998) Cloning and sequencing of four new mammalian monocarboxylate transporter homologues confirms the existence of a transporter family with an ancient past. Biochem J 329:321–328
Crossref
PubMed
ISI
Google Scholar
Reed LJ, Marsden P, Lasserson D, Sheldon N, Lewis P, Stanhope N, Guinan E, Kopelman MD (1999) FDG-PET analysis and findings in amnesia resulting from hypoxia. Memory 3:599–612
Crossref
ISI
Google Scholar
Reivich M, Alavi A, Wolf A, Fowler J, Russell J, Arnett C, MacGregor RR, Shine CY, Atkins H, Anand A (1985) Glucose metabolic rate kinetic model parameter determination in humans: the lumped constants and rate constants for 18-fluorodeoxyglucose and 11-C-deoxyglucose. J Cereb Blood Flow Metab 5:179–192
Crossref
PubMed
ISI
Google Scholar
Siesjo BK (1978) Utilisation of substrates by brain tissues. In: Brain energy metabolism, New York: Wiley, pp 101–130
Google Scholar
Schurr A, West CA, Rigor BM (1988) Lactate-supported synaptic function in the rat hippocampal slice preparation. Science 240:1326–1328
Crossref
PubMed
ISI
Google Scholar
Schurr A, Payne RS, Miller JJ, Rigor BM (1997) Glia are the main source of lactate utilized by neurons for recovery of function posthypoxia. Brain Res 774:221–224
Crossref
PubMed
ISI
Google Scholar
Schurr A, Miller JJ, Payne RS, Rigor BM (1999) An increase in lactate output by brain tissue serves to meet the energy needs of glutamate-activated neurons. J Neurosci 19:34–39
Crossref
PubMed
ISI
Google Scholar
Shackford SR, Zhuang J, Schmoker J (1992) Intravenous fluid tonicity: effect on intracranial pressure, cerebral blood flow, and cerebral oxygen delivery in focal brain injury. J Neurosurg 76:91–98
Crossref
PubMed
ISI
Google Scholar
Stanley W, Gertz E, Wisneski J, Morris L, Neese R, Brooks G (1985) Systemic lactate kinetics during graded exercise in man. Am J Physiol 249:E595–E602
PubMed
ISI
Google Scholar
Stittsworth JD, Lanthorn TH (1993) Lactate mimics only some effects of D-glucose on epileptic depolarization and long-term synaptic failure. Brain Res 630:21–27
Crossref
PubMed
ISI
Google Scholar
Studholme C, Hill DLG, Hawkes DJ (1997) Automated 3-D: registration of magnetic resonance and positron emission tomography brain slices by multi-resolution optimisation of voxel similarity measures. Med Phys 24:25–35
Crossref
PubMed
ISI
Google Scholar
Taberno A, Vicario C, Medin JM (1996) Lactate spares glucose as a metabolic fuel in neurons and astrocytes from primary culture. Neurosci Res 26:369–376
Crossref
PubMed
ISI
Google Scholar
Tildon JT, McKenna MC, Stevenson J, Couto R (1993) Transport of L-lactate by cultured rat brain astrocytes. Neurochem Res 18:177–184
Crossref
PubMed
ISI
Google Scholar
Veneman T, Mitrakou A, Mokan M, Cryer P, Gerich J (1994) Effect of hyperketonemia and hyperlacticacidemia on symptoms, cognitive dysfunction and counterregulatory hormone responses during hypoglycaemia in normal humans. Diabetes 43:1311–1317
Crossref
PubMed
ISI
Google Scholar
Walz W, Mukerji S (1990) Simulation of aspects of ischemia in cell culture: changes in lactate compartmentation. Glia 3:522–528
Crossref
PubMed
ISI
Google Scholar

Cite article

Cite article

Cite article

OR

Download to reference manager

If you have citation software installed, you can download article citation data to the citation manager of your choice

Share options

Share

Share this article

Share with email
EMAIL ARTICLE LINK
Share on social media

Share access to this article

Sharing links are not relevant where the article is open access and not available if you do not have a subscription.

For more information view the Sage Journals article sharing page.

Information, rights and permissions

Information

Published In

Volume 23, Issue 6
Pages: 658 - 664
Article first published: June 2003
Issue published: June 2003

Keywords

  1. 18Fluoro-deoxyglucose
  2. Positron emission tomography
  3. Region of interest
  4. Statistical parametric mapping

Rights and permissions

© 2003 The International Society for Cerebral Blood Flow and Metabolism.
Request permissions for this article.
PubMed: 12796713

Authors

Affiliations

Diarmuid Smith
Department of Diabetes, Endocrinology and Internal Medicine, School of Medicine, King's College, London, United Kingdom
View all articles by this author
Andrew Pernet
Department of Diabetes, Endocrinology and Internal Medicine, School of Medicine, King's College, London, United Kingdom
View all articles by this author
William A. Hallett
The Clinical PET Center, Guy's Kings and St Thomas', School of Medicine, King's College, London, United Kingdom
View all articles by this author
Emma Bingham
Department of Diabetes, Endocrinology and Internal Medicine, School of Medicine, King's College, London, United Kingdom
View all articles by this author
Paul K. Marsden
The Clinical PET Center, Guy's Kings and St Thomas', School of Medicine, King's College, London, United Kingdom
View all articles by this author
Stephanie A. Amiel
Department of Diabetes, Endocrinology and Internal Medicine, School of Medicine, King's College, London, United Kingdom
[email protected]
View all articles by this author

Notes

Address correspondence and reprint requests to Professor Stephanie Amiel, Department of Diabetes, Endocrinology and Internal Medicine, Guy's, King's and St Thomas' School of Medicine, King's College Denmark Hill Campus, Bessemer Road, London SE5 9PJ, United Kingdom; e-mail: [email protected]
This study was funded by Diabetes U.K.

Metrics and citations

Metrics

Journals metrics

This article was published in Journal of Cerebral Blood Flow & Metabolism.

VIEW ALL JOURNAL METRICS

Article usage*

Total views and downloads: 3013

*Article usage tracking started in December 2016

Altmetric

See the impact this article is making through the number of times it’s been read, and the Altmetric Score.
Learn more about the Altmetric Scores


Articles citing this one

Receive email alerts when this article is cited

Web of Science: 204 view articles Opens in new tab

Crossref: 213

  1. Potentially compromised systemic and local lactate metabolic balance i...
    Go to citation Crossref Google Scholar
  2. Hippocampal Lactate-Infusion Enhances Spatial Memory Correlated with M...
    Go to citation Crossref Google Scholar
  3. Glutamine Alleviates I/R-Induced Intestinal Injury and Dysmotility Via...
    Go to citation Crossref Google Scholar
  4. Magnetic resonance spectroscopy in the hippocampus of adult APP/PS1 mi...
    Go to citation Crossref Google Scholar
  5. Involvement of Astrocytes in the Formation, Maintenance, and Function ...
    Go to citation Crossref Google Scholar
  6. Astrocyte-neuron lactate shuttle plays a pivotal role in sensory-based...
    Go to citation Crossref Google Scholar
  7. CD300f immune receptor contributes to healthy aging by regulating infl...
    Go to citation Crossref Google Scholar
  8. A new perspective on HIV: effects of HIV on brain-heart axis
    Go to citation Crossref Google Scholar
  9. Global-Scale Profiling of Differential Expressed Lysine-Lactylated Pro...
    Go to citation Crossref Google Scholar
  10. Metabolomics in aging research: aging markers from organs
    Go to citation Crossref Google Scholar
  11. Lactate shuttling as an allostatic means of thermoregulation in the br...
    Go to citation Crossref Google Scholar
  12. The Key Role of Mitochondrial Function in Health and Disease
    Go to citation Crossref Google Scholar
  13. In vivo calibration of genetically encoded metabolite biosensors must ...
    Go to citation Crossref Google Scholar
  14. Neurovascular development
    Go to citation Crossref Google Scholar
  15. Lactate-Mediated Signaling in the Brain—An Update
    Go to citation Crossref Google Scholar
  16. Brain metabolic responses to cannabis use in people with multiple scle...
    Go to citation Crossref Google Scholar
  17. Cannabis and Multiple Sclerosis
    Go to citation Crossref Google Scholar
  18. Effects of Elevated Intraocular Pressure on Retinal Ganglion Cell Dens...
    Go to citation Crossref Google Scholar
  19. Lymphoma total lesion glycolysis leads to hyperlactatemia and reductio...
    Go to citation Crossref Google Scholar
  20. Astrocyte-derived lactate/NADH alters methamphetamine-induced memory c...
    Go to citation Crossref Google Scholar
  21. Activation of brain lactate receptor GPR81 aggravates exercise-induced...
    Go to citation Crossref Google Scholar
  22. Monocarboxylate transporters (MCTs) in skeletal muscle and hypothalamu...
    Go to citation Crossref Google Scholar
  23. Lactate-Dependent Cross-Talk Between Astrocyte and GnRH-I Neurons in H...
    Go to citation Crossref Google Scholar
  24. Tracing the lactate shuttle to the mitochondrial reticulum
    Go to citation Crossref Google Scholar
  25. Brain Energy Metabolism in Ischemic Stroke: Effects of Smoking and Dia...
    Go to citation Crossref Google Scholar
  26. Uncooked cornstarch for the prevention of hypoglycemic events
    Go to citation Crossref Google Scholar
  27. Association between preoperative serum lactate concentrate with tumor ...
    Go to citation Crossref Google Scholar
  28. Brain Metabolic Alterations in Alzheimer’s Disease
    Go to citation Crossref Google Scholar
  29. Oral lactate slows gastric emptying and suppresses appetite in young m...
    Go to citation Crossref Google Scholar
  30. Astrocytes as Key Regulators of Brain Energy Metabolism: New Therapeut...
    Go to citation Crossref Google Scholar
  31. Aerobic Glycolysis: A DeOxymoron of (Neuro)Biology
    Go to citation Crossref Google Scholar
  32. APOΕ4 lowers energy expenditure in females and impairs glucose oxidati...
    Go to citation Crossref Google Scholar
  33. Mitochondrial Transport in Glycolysis and Gluconeogenesis: Achievement...
    Go to citation Crossref Google Scholar
  34. Effect of Exercise on Brain Health: The Potential Role of Lactate as a...
    Go to citation Crossref Google Scholar
  35. Lactate transporters in the rat barrel cortex sustain whisker-dependen...
    Go to citation Crossref Google Scholar
  36. Metabolomic signature of the Dravet syndrome: A genetic mouse model st...
    Go to citation Crossref Google Scholar
  37. Dietary medium chain triglycerides for management of epilepsy: New dat...
    Go to citation Crossref Google Scholar
  38. Reactive astrocytes: The nexus of pathological and clinical hallmarks ...
    Go to citation Crossref Google Scholar
  39. Glucocorticoids, metabolism and brain activity
    Go to citation Crossref Google Scholar
  40. Nutritional factors in sport-related concussion
    Go to citation Crossref Google Scholar
  41. Role of the Heart in Lactate Shuttling
    Go to citation Crossref Google Scholar
  42. Alternative Cerebral Fuels in the First Five Days in Healthy Term Infa...
    Go to citation Crossref Google Scholar
  43. Noradrenaline‐induced l ‐lactate productio...
    Go to citation Crossref Google Scholar
  44. Voluntary Wheel Running Did Not Alter Gene Expression in 5xfad Mice, b...
    Go to citation Crossref Google Scholar
  45. High-speed label-free two-photon fluorescence microscopy of metabolic ...
    Go to citation Crossref Google Scholar
  46. Confirmed Hypoglycemia Without Whipple Triad: A Rare Case of Hyper-War...
    Go to citation Crossref Google Scholar
  47. Lactate consumption mediates repeated high-intensity interval exercise...
    Go to citation Crossref Google Scholar
  48. Long-term Ashtanga yoga practice decreases medial temporal and brainst...
    Go to citation Crossref Google Scholar
  49. Mitochondrial Metabolism in Astrocytes Regulates Brain Bioenergetics, ...
    Go to citation Crossref Google Scholar
  50. The tortuous path of lactate shuttle discovery: From cinders and board...
    Go to citation Crossref Google Scholar
  51. Phosphoglycerate mutase 1 reduces neuronal damage in the hippocampus f...
    Go to citation Crossref Google Scholar
  52. Extended preclinical investigation of lactate for neuroprotection afte...
    Go to citation Crossref Google Scholar
  53. Cerebrospinal fluid and blood lactate concentrations as prognostic bio...
    Go to citation Crossref Google Scholar
  54. Effects of psychosocial and physical stress on lactate and anxiety lev...
    Go to citation Crossref Google Scholar
  55. Effect of lactate administration on brain lactate levels during hypogl...
    Go to citation Crossref Google ScholarPub Med
  56. The energetic brain – A review from students to students
    Go to citation Crossref Google Scholar
  57. L-Lactate Promotes Adult Hippocampal Neurogenesis
    Go to citation Crossref Google Scholar
  58. Chronic, low-level oral exposure to marine toxin, domoic acid, alters ...
    Go to citation Crossref Google Scholar
  59. Metabolism and inflammation: implications for traumatic brain injury t...
    Go to citation Crossref Google Scholar
  60. FOXK1 and FOXK2 regulate aerobic glycolysis
    Go to citation Crossref Google Scholar
  61. Development of a Model to Test Whether Glycogenolysis Can Support Astr...
    Go to citation Crossref Google Scholar
  62. Brain Tumors of Glial Origin
    Go to citation Crossref Google Scholar
  63. The rat cumulative allostatic load measure (rCALM): a new translationa...
    Go to citation Crossref Google Scholar
  64. Essential Roles of Lactate in Müller Cell Survival and Function
    Go to citation Crossref Google Scholar
  65. p66Shc activation promotes increased oxidative phosphorylation and ren...
    Go to citation Crossref Google Scholar
  66. Glycolysis Paradigm Shift Dictates a Reevaluation of Glucose and Oxyge...
    Go to citation Crossref Google Scholar
  67. Short-term interval training alters brain glucose metabolism in subjec...
    Go to citation Crossref Google ScholarPub Med
  68. Multiple Sclerosis, Cannabis Use, and Clinical Disability: A Prelimina...
    Go to citation Crossref Google Scholar
  69. Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availabil...
    Go to citation Crossref Google Scholar
  70. Age related rise in lactate and its correlation with lactate dehydroge...
    Go to citation Crossref Google Scholar
  71. Electrical Control in Neurons by the Ketogenic Diet
    Go to citation Crossref Google Scholar
  72. Hypertonic sodium lactate reverses brain oxygenation and metabolism dy...
    Go to citation Crossref Google Scholar
  73. Lactate metabolism: historical context, prior misinterpretations, and ...
    Go to citation Crossref Google Scholar
  74. The Science and Translation of Lactate Shuttle Theory
    Go to citation Crossref Google Scholar
  75. Lactate in the brain: from metabolic end-product to signalling molecul...
    Go to citation Crossref Google Scholar
  76. Lactate supplementation in severe traumatic brain injured adults by pr...
    Go to citation Crossref Google Scholar
  77. Maintained exercise‐enhanced brain executive function related to cereb...
    Go to citation Crossref Google Scholar
  78. Lead-Induced Developmental Neurotoxicity and Modulated Gene Expression
    Go to citation Crossref Google Scholar
  79. Oral lactate intensifies insulin toxicity during severe insulin-induce...
    Go to citation Crossref Google Scholar
  80. Neuroprotective effect of bispectral index-guided fast-track anesthesi...
    Go to citation Crossref Google Scholar
  81. The Oxygen Paradox, the French Paradox, and age-related diseases
    Go to citation Crossref Google Scholar
  82. The Elusive Path of Brain Tissue Oxygenation and Cerebral Perfusion in...
    Go to citation Crossref Google Scholar
  83. Food for thought: Impact of metabolism on neuronal excitability
    Go to citation Crossref Google Scholar
  84. Hyperpalatable Diet and Physical Exercise Modulate the Expression of t...
    Go to citation Crossref Google Scholar
  85. Loss of Brain Aerobic Glycolysis in Normal Human Aging
    Go to citation Crossref Google Scholar
  86. A Single Bout of High-Intensity Interval Training Reduces Awareness of...
    Go to citation Crossref Google Scholar
  87. Lactate Shuttles in Neuroenergetics—Homeostasis, Allostasis and Beyond
    Go to citation Crossref Google Scholar
  88. Lactate in the brain: an update on its relevance to brain energy, neur...
    Go to citation Crossref Google ScholarPub Med
  89. Do Reported Effects of Acute Aerobic Exercise on Subsequent Higher Cog...
    Go to citation Crossref Google Scholar
  90. Neural–metabolic coupling in the central visual pathway
    Go to citation Crossref Google Scholar
  91. The impact of age on cerebral perfusion, oxygenation and metabolism du...
    Go to citation Crossref Google Scholar
  92. Glutamate excitotoxicity and Ca 2+ -regulation of respiration: Role of...
    Go to citation Crossref Google Scholar
  93. l-Lactate-Mediated Neuroprotection against Glutamate-Induced Excitotox...
    Go to citation Crossref Google Scholar
  94. Cerebral Lactate Metabolism After Traumatic Brain Injury
    Go to citation Crossref Google Scholar
  95. Evaluation of in vivo mitochondrial bioenergetics in skeletal muscle u...
    Go to citation Crossref Google Scholar
  96. Improvement of Neuroenergetics by Hypertonic Lactate Therapy in Patien...
    Go to citation Crossref Google Scholar
  97. AMPK Signalling and Defective Energy Metabolism in Amyotrophic Lateral...
    Go to citation Crossref Google Scholar
  98. Lactato de sodio 0,5 molar: ¿el agente osmótico que buscamos?
    Go to citation Crossref Google Scholar
  99. Lactate and its many faces
    Go to citation Crossref Google Scholar
  100. A Case of Malignancy-induced Lactic Acidosis Having Difficulty with Di...
    Go to citation Crossref Google Scholar
  101. Neuroprotection in acute brain injury: an up-to-date review
    Go to citation Crossref Google Scholar
  102. Energy Metabolism of the Brain, Including the Cooperation between Astr...
    Go to citation Crossref Google Scholar
  103. Neurometabolic coupling between neural activity, glucose, and lactate ...
    Go to citation Crossref Google Scholar
  104. Brain energy metabolism measured by 13 C ...
    Go to citation Crossref Google Scholar
  105. A Cellular Perspective on Brain Energy Metabolism and Functional Imagi...
    Go to citation Crossref Google Scholar
  106. Walking Speed and Brain Glucose Uptake are Uncoupled in Patients with ...
    Go to citation Crossref Google Scholar
  107. Cerebral metabolism following traumatic brain injury: new discoveries ...
    Go to citation Crossref Google Scholar
  108. Lactate Transport and Signaling in the Brain: Potential Therapeutic Ta...
    Go to citation Crossref Google ScholarPub Med
  109. Monocarboxylate transporters in temporal lobe epilepsy: roles of lacta...
    Go to citation Crossref Google Scholar
  110. Lactate activates the somatotropic axis in rats
    Go to citation Crossref Google Scholar
  111. Acute exercise improves motor memory: Exploring potential biomarkers
    Go to citation Crossref Google Scholar
  112. Bioartificial livers in vitro and ...
    Go to citation Crossref Google Scholar
  113. Cerebral glycolysis: a century of persistent misunderstanding and misc...
    Go to citation Crossref Google Scholar
  114. Lactate Receptor Sites Link Neurotransmission, Neurovascular Coupling,...
    Go to citation Crossref Google Scholar
  115. Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate p...
    Go to citation Crossref Google Scholar
  116. Rise of ketone bodies with psychosocial stress in normal weight men
    Go to citation Crossref Google Scholar
  117. Lactate and the injured brain
    Go to citation Crossref Google Scholar
  118. Banting Memorial Lecture 2013 A life in balance: wanderi...
    Go to citation Crossref Google Scholar
  119. Cerebral metabolic effects of exogenous lactate supplementation on the...
    Go to citation Crossref Google Scholar
  120. Brain lactate in hepatic encephalopathy: Friend or foe?
    Go to citation Crossref Google Scholar
  121. Role of Energy Metabolic Deficits and Oxidative Stress in Excitotoxic ...
    Go to citation Crossref Google ScholarPub Med
  122. Glial Glutamate and Metabolic Transporters as a Target for Neurodegene...
    Go to citation Crossref Google Scholar
  123. Carbon (13C) MRS
    Go to citation Crossref Google Scholar
  124. Hypoglycemia in the toddler and child
    Go to citation Crossref Google Scholar
  125. Lactate Uptake by the Injured Human Brain: Evidence from an Arterioven...
    Go to citation Crossref Google Scholar
  126. Beyond intracranial pressure: optimization of cerebral blood flow, oxy...
    Go to citation Crossref Google Scholar
  127. Cerebral Extracellular Lactate Increase is Predominantly Nonischemic i...
    Go to citation Crossref Google ScholarPub Med
  128. Increased Brain Lactate Concentrations Without Increased Lactate Oxida...
    Go to citation Crossref Google Scholar
  129. Spatial expression and functional flexibility of monocarboxylate trans...
    Go to citation Crossref Google Scholar
  130. Exhausting exercise and tissue-specific expression of monocarboxylate ...
    Go to citation Crossref Google Scholar
  131. Reevaluating Metabolism in Alzheimer's Disease from the Perspective of...
    Go to citation Crossref Google Scholar
  132. Temporal dynamics of lactate concentration in the human brain during a...
    Go to citation Crossref Google Scholar
  133. Patients with type 1 diabetes exhibit altered cerebral metabolism duri...
    Go to citation Crossref Google Scholar
  134. Adenosine and Energy Metabolism—Relationship to Brain Bioenergetics
    Go to citation Crossref Google Scholar
  135. Revisiting Lactate in Critical Illness
    Go to citation Crossref Google Scholar
  136. D-Lactate altered mitochondrial energy production in rat brain and hea...
    Go to citation Crossref Google Scholar
  137. “Hyper-Warburgism,” a Cause of Asymptomatic Hypoglycemia with Lactic A...
    Go to citation Crossref Google Scholar
  138. The Central Role of Astrocytes in Neuroenergetics
    Go to citation Crossref Google Scholar
  139. Poly(amido)amine dendrimers generation 4.0 (PAMAM G4) reduce blood hyp...
    Go to citation Crossref Google Scholar
  140. Mitochondria in traumatic brain injury and mitochondrial‐targeted mult...
    Go to citation Crossref Google Scholar
  141. Fueling and Imaging Brain Activation
    Go to citation Crossref Google ScholarPub Med
  142. Sweet Sixteen for ANLS
    Go to citation Crossref Google ScholarPub Med
  143. Brain Lactate Metabolism: The Discoveries and the Controversies
    Go to citation Crossref Google ScholarPub Med
  144. Lactate infusion during euglycemia but not hypoglycemia reduces subseq...
    Go to citation Crossref Google Scholar
  145. Acute feedback control of astrocytic glycolysis by lactate
    Go to citation Crossref Google Scholar
  146. Physiological oxygen level is critical for modeling neuronal metabolis...
    Go to citation Crossref Google Scholar
  147. The Coupling of Cerebral Metabolic Rate of Glucose and Cerebral Blood ...
    Go to citation Crossref Google Scholar
  148. Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic Cooperati...
    Go to citation Crossref Google Scholar
  149. 13 C MRS studies of neuroenergetics and neurotransmitter...
    Go to citation Crossref Google Scholar
  150. Cerebral glucose and lactate consumption during cerebral activation by...
    Go to citation Crossref Google Scholar
  151. Brain energy depletion in a rodent model of diffuse traumatic brain in...
    Go to citation Crossref Google Scholar
  152. Effect of Acute Hypoglycemia on Human Cerebral Glucose Metabolism Meas...
    Go to citation Crossref Google Scholar
  153. Acute Depression of Energy Metabolism after Microdialysis Probe Implan...
    Go to citation Crossref Google Scholar
  154. Cerebral Blood Flow and Metabolism and Cerebral Ischemia
    Go to citation Crossref Google Scholar
  155. Hypoxia stimulates lactate disposal in rainbow trout
    Go to citation Crossref Google Scholar
  156. Increase brain lactate in hepatic encephalopathy: Cause or consequence...
    Go to citation Crossref Google Scholar
  157. The Contribution of Blood Lactate to Brain Energy Metabolism in Humans...
    Go to citation Crossref Google Scholar
  158. Food for thought: the importance of glucose and other energy substrate...
    Go to citation Crossref Google Scholar
  159. Low plasma lactate concentration as a biomarker of an incompetent brai...
    Go to citation Crossref Google Scholar
  160. Cerebral Blood Flow Response to Functional Activation
    Go to citation Crossref Google ScholarPub Med
  161. Heavy Metal-Regulated Gene Expression
    Go to citation Crossref Google Scholar
  162. Tumor metabolism of lactate: the influence and therapeutic potential f...
    Go to citation Crossref Google Scholar
  163. The human brain utilizes lactate via the tricarboxylic acid cycle: a 1...
    Go to citation Crossref Google Scholar
  164. Hypoglycemia: From the Laboratory to the Clinic
    Go to citation Crossref Google Scholar
  165. Elevated brain lactate responses to neural activation in panic disorde...
    Go to citation Crossref Google Scholar
  166. Production of panic-like symptoms by lactate is associated with increa...
    Go to citation Crossref Google Scholar
  167. Lactate overrides central nervous but not β-cell glucose sensing in hu...
    Go to citation Crossref Google Scholar
  168. Basal and stimulated lactate fluxes in primary cultures of astrocytes ...
    Go to citation Crossref Google Scholar
  169. Distribution of the monocarboxylate transporter MCT2 in human cerebral...
    Go to citation Crossref Google Scholar
  170. Unlocking the Energy Dynamics of Executive Functioning: Linking Execut...
    Go to citation Crossref Google ScholarPub Med
  171. Management of Hyperglycemia in Acute Stroke
    Go to citation Crossref Google Scholar
  172. Prevention of Hypoglycemia While Achieving Good Glycemic Control in Ty...
    Go to citation Crossref Google Scholar
  173. Differential energetic response of brain vs. skeletal muscle upon glyc...
    Go to citation Crossref Google Scholar
  174. The brain at work: A cerebral metabolic manifestation of central fatig...
    Go to citation Crossref Google Scholar
  175. A method to measure lactate recycling in cultured cells by edited 1H n...
    Go to citation Crossref Google Scholar
  176. Effect of lactate therapy upon cognitive deficits after traumatic brai...
    Go to citation Crossref Google Scholar
  177. Activity‐dependent regulation of energy metabolism by astrocytes: An u...
    Go to citation Crossref Google Scholar
  178. Enhanced expression of three monocarboxylate transporter isoforms in t...
    Go to citation Crossref Google Scholar
  179. Lactate, not pyruvate, is neuronal aerobic glycolysis end product: An ...
    Go to citation Crossref Google Scholar
  180. Kinetic Parameters and Lactate Dehydrogenase Isozyme Activities Suppor...
    Go to citation Crossref Google Scholar
  181. Systemic lupus erythematosus and the brain: What mice are telling us
    Go to citation Crossref Google Scholar
  182. Regulation of Cerebral Blood Flow During Exercise
    Go to citation Crossref Google Scholar
  183. Effectiveness of extracellular lactate/pyruvate for sustaining synapti...
    Go to citation Crossref Google Scholar
  184. Pioglitazone does not increase cerebral glucose utilisation in a murin...
    Go to citation Crossref Google Scholar
  185. Fuelling Cerebral Activity in Exercising Man
    Go to citation Crossref Google ScholarPub Med
  186. Lactate: The Ultimate Cerebral Oxidative Energy Substrate?
    Go to citation Crossref Google ScholarPub Med
  187. Expression of the monocarboxylate transporter MCT1 in the adult human ...
    Go to citation Crossref Google Scholar
  188. A fast and sensitive 1 H NMR method to mea...
    Go to citation Crossref Google Scholar
  189. High intensity exercise decreases global brain glucose uptake in human...
    Go to citation Crossref Google Scholar
  190. Hypoglycaemia and cognitive function
    Go to citation Crossref Google Scholar
  191. Understanding of cerebral energy metabolism by dynamic living brain sl...
    Go to citation Crossref Google Scholar
  192. Monocarboxylate transporters in the central nervous system: distributi...
    Go to citation Crossref Google Scholar
  193. Measurement of Regional Rates of Cerebral Protein Synthesis with L-[1-...
    Go to citation Crossref Google ScholarPub Med
  194. Severe cognitive impairment correlates with higher cerebrospinal fluid...
    Go to citation Crossref Google Scholar
  195. Hematological and acid-base changes in men during prolonged exercise w...
    Go to citation Crossref Google Scholar
  196. Ampakine™ CX546 bolsters energetic response of astrocytes: a novel tar...
    Go to citation Crossref Google Scholar
  197. Differential Effects of Glucose and Lactate on Glucosensing Neurons in...
    Go to citation Crossref Google Scholar
  198. Cellular and subcellular distribution of monocarboxylate transporters ...
    Go to citation Crossref Google Scholar
  199. Futile cycling of lactate through the plasma membrane of C6 glioma cel...
    Go to citation Crossref Google Scholar
  200. On-line monitoring of striatum glucose and lactate in the endothelin-1...
    Go to citation Crossref Google Scholar
  201. Insulin therapy and hypoglycaemia: the size of the problem
    Go to citation Crossref Google Scholar
  202. Cerebral metabolism during upper and lower body exercise
    Go to citation Crossref Google Scholar
  203. Metabolic stages, mitochondria and calcium in hypoxic/ischemic brain d...
    Go to citation Crossref Google Scholar
  204. Cerebral carbohydrate cost of physical exertion in humans
    Go to citation Crossref Google Scholar
  205. Dual-Gene, Dual-Cell Type Therapy against an Excitotoxic Insult by Bol...
    Go to citation Crossref Google Scholar
  206. Lactate metabolism: a new paradigm for the third millennium
    Go to citation Crossref Google Scholar
  207. Brain glycogen re‐awakened
    Go to citation Crossref Google Scholar
  208. Neuroenergetics: Calling Upon Astrocytes to Satisfy Hungry Neurons
    Go to citation Crossref Google ScholarPub Med
  209. Increased lactate/pyruvate ratio augments blood flow in physiologicall...
    Go to citation Crossref Google Scholar
  210. A reduced cerebral metabolic ratio in exercise reflects metabolism and...
    Go to citation Crossref Google Scholar
  211. Lactate is a Preferential Oxidative Energy Substrate over Glucose for ...
    Go to citation Crossref Google ScholarPub Med
  212. Food for Thought: Challenging the Dogmas
    Go to citation Crossref Google ScholarPub Med
  213. Mitochondrial Disease
    Go to citation Crossref Google Scholar

Figures and tables

Figures & Media

Tables

View Options

View options

PDF/ePub

View PDF/ePub

Get access

Access options

If you have access to journal content via a personal subscription, university, library, employer or society, select from the options below:

ISCBFM members can access this journal content using society membership credentials.

MEMBERSHIP LOGIN

ISCBFM members can access this journal content using society membership credentials.

MEMBERSHIP LOGIN

Alternatively, view purchase options below:

Purchase 24 hour online access to view and download content.

Subscribe to this journal

Access journal content via a DeepDyve subscription or find out more about this option.

Start 2 week free trial
Need help?

Also from Sage