Lactate production by human monocytes/macrophages determined by proton mr spectroscopy

López‐Villegas, Dolores; Lenkinski, Robert E.; Wehrli, Suzanne; Ho, Wen‐Zhe; Douglas, Steven D.

doi:10.1002/mrm.1910340107

Cited by 70 publications

(37 citation statements)

References 36 publications

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“…Following resuscitation, it decreases, but due to the secondary energy failure it increases again after 24 h (5, 37). Elevated Lac levels have been shown until months after the hypoxiaischemia, probably due to an influx of Lac-producing macrophages in the damaged tissue or an altered redox state (36,38,39). Lac/NAA was significantly elevated in the group with abnormal outcome, as in previous reports (1,6,32,40,41).…”

Section: Discussionsupporting

confidence: 80%

Value of 1H-MRS Using Different Echo Times in Neonates with Cerebral Hypoxia-Ischemia

2001

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Previous studies have shown altered brain metabolism after cerebral hypoxia-ischemia, using magnetic resonance spectroscopy with echo times (TE) of 272 and 136 ms, based on peak-area or peak-height ratios. The present study examined the additional value of proton magnetic resonance spectroscopy with a short TE (31 ms) to predict a poor outcome in neonates with brain hypoxia-ischemia. Studies were performed in 21 full-term neonates with perinatal asphyxia in a 1.5 tesla magnetic field. Proton magnetic resonance spectroscopy was performed in a single volume of interest including the basal ganglia. TE of 272, 136 and 31 ms were used. After curve-fitting procedures, peakareas as well as peak-height ratios of different brain metabolites were calculated, comparing patients with a poor versus a good outcome. Seven neonates out of 21 had a poor outcome. Neonates with a poor outcome showed a significantly lower Nacetylaspartate/choline (NAA/Cho) and a significantly raised lactate/NAA (Lac/NAA) ratio using TE of 272 and 136 ms. Using a TE of 31 ms, no differences were found in glutamate/ NAA (Glx/NAA), Glx/Cho, myo-inositol/NAA (mI/NAA), and mI/Cho ratios between neonates with a good and those with a poor outcome. Highest predictive values could be achieved for NAA/Cho with a TE of 136 ms. We conclude that low NAA/Cho and high Lac/NAA ratios predict a poor outcome in neonates with cerebral hypoxia-ischemia. Previous studies have shown changes in the cerebral metabolism of human neonates and of animals following hypoxiaischemia (1-5). Using 1 H-MRS, decreases in NAA/Cho and NAA/Cr ratios were noted to predict poor neurodevelopment (1). An increased brain Lac, which, under normal circumstances, is present in only very small amounts in the neonatal brain and is hardly detectable by 1 H-MRS at term age, also predicts a poor outcome (3, 6). These studies used TE of 272 or 136 ms (1, 2, 4, 6). Using a TE of 272 ms, the peak at 1.33 ppm represents Lac. Using a TE of 136 ms, the Lac peak will be inverted, thereby distinguishing between Lac and lipids or macromolecules. Due to coupling effects, the amplitude of the Lac peak is expected to be smaller at TE 136 ms compared with TE 272 ms (7). Secondly, T2 values for NAA, Cho, and Cr differ (8, 9), and thereby differences in NAA/Cho or NAA/Cr ratios between good outcome and poor outcome groups might be more prominent at certain TE. In addition, T2 values may change following cerebral hypoxia-ischemia (10). Therefore, differences in metabolite ratios might be more prominent at longer TE. In fact, a recent study demonstrated a better predictive value for a long TE (270 ms) versus a short TE (20 ms) in occipital gray matter of young children (11).With shorter TE, e.g. 30 ms, lipids and macromolecules can be identified. Especially in ischemic brain areas, these metabolites with resonances of 0.9 -1.3 ppm will be elevated massively, thereby complicating the detection of lactate at 1.33 ppm (12

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Section: Discussionsupporting

confidence: 80%

Value of 1H-MRS Using Different Echo Times in Neonates with Cerebral Hypoxia-Ischemia

2001

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“…Increased lactate can result from several potential mechanisms, such as post-injury increases in glycolysis (Kawamata et al, 1995;Yoshino et al, 1991) and reduced oxidative metabolism, with oxidative injury to key metabolic enzymes (Bogaert et al, 2000;Kochanek et al, 2006;Martin et al, 2005;Opii et al, 2007;Richards et al, 2006;Robertson et al, 2007). Another source of lactate after TBI is from infiltration of inflammatory cells, such as macrophages (Lopez-Villegas et al, 1995;Schuhmann et al, 2003;Petroff et al, 1992). In addition, astrocytes can produce lactate, serving as a post-traumatic energy substrate for nearby neurons (Pellerin et al, 1998;Schuhmann et al, 2003;Soustiel et al, 2005;McKenna et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Early and Sustained Alterations in Cerebral Metabolism after Traumatic Brain Injury in Immature Rats

Casey

McKenna

Fiskum

et al. 2008

Journal of Neurotrauma

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Although studies have shown alterations in cerebral metabolism after traumatic brain injury (TBI), clinical data in the developing brain is limited. We hypothesized that post-traumatic metabolic changes occur early (Ͻ24 h) and persist for up to 1 week. Immature rats underwent TBI to the left parietal cortex. Brains were removed at 4 h, 24 h, and 7 days after injury, and separated into ipsilateral (injured) and contralateral (control) hemispheres. Proton nuclear magnetic resonance (NMR) spectra were obtained, and spectra were analyzed for N-acetyl-aspartate (NAA), lactate (Lac), creatine (Cr), choline, and alanine, with metabolite ratios determined (NAA/Cr, Lac/Cr). There were no metabolic differences at any time in sham controls between cerebral hemispheres. At 4 and 24 h, there was an increase in Lac/Cr, reflecting increased glycolysis and/or decreased oxidative metabolism. At 24 h and 7 days, there was a decrease in NAA/Cr, indicating loss of neuronal integrity. The NAA/Lac ratio was decreased (ϳ15-20%) at all times (4 h, 24 h, 7 days) in the injured hemisphere of TBI rats. In conclusion, metabolic derangements begin early (Ͻ24 h) after TBI in the immature rat and are sustained for up to 7 days. Evaluation of early metabolic alterations after TBI could identify novel targets for neuroprotection in the developing brain.

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“…Pathology from a patient who died shortly after MRS examination 6 as well as neuropathology studies of the natural evolution of a cerebral infarct 17,18 suggest that, at least in the subacute period, the lipids may reside within macrophages. Leukocytes are known to produce lactate even under aerobic conditions 7,19 and contain prominent lipid peaks when activated. 11 If borne out by further studies, the combined assessment of both lactate and lipid within infarcted brain may provide a noninvasive way to monitor the inflammatory response after stroke.…”

Section: Discussionmentioning

confidence: 99%

“…While lactate is produced acutely by ischemia, lactate seen beyond the first 72 hours may reflect the presence of macrophages and other leukocytes. 6,7 Previous studies 2,8 used long echo times (TEs) of 270 ms to optimize lactate and eliminate coresonant lipid signals. However, the use of long TEs has several drawbacks.…”

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confidence: 99%

Spectroscopic Assessment of Alterations in Macromolecule and Small-Molecule Metabolites in Human Brain After Stroke

Graham

Hwang

Rothman

et al. 2001

Stroke

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Background and Purpose-We sought to measure the temporal evolution and spatial distribution of lesion macromolecules and small molecules (lactate, N-acetyl compounds, creatine, and choline) in stroke patients by using short echo time in vivo proton MR spectroscopy. Methods-Single-voxel spectra with TEϭ22 ms were obtained with and without inversion recovery suppression of small-molecule resonances from 30 examinations of 24 patients 3 to 214 days after stroke. Subtraction of the suppressed from the unsuppressed spectra yielded metabolite spectra without overlap from macromolecules. Two-dimensional spectroscopic images were acquired with macromolecule and small-molecule suppression from 5 additional patients. Results-Macromolecule signals were elevated in lesions relative to normal brain and tended to increase in the subacute period, even as lactate peaks declined. Regions of increased lactate, increased macromolecule signal at 1.3 ppm, and decreased N-acetyl compounds were closely correlated in the 2D spectroscopic images. Key Words: nuclear magnetic resonance Ⅲ lipids Ⅲ lactic acid Ⅲ cerebral infarction Ⅲ cerebrovascular accident I n vivo proton magnetic resonance spectroscopy (MRS) has consistently detected elevated brain lactate after human stroke that may persist for many months. [1][2][3][4][5] The origin and significance of this lactate may vary at different times during the evolution of the infarct. While lactate is produced acutely by ischemia, lactate seen beyond the first 72 hours may reflect the presence of macrophages and other leukocytes. 6,7 Previous studies 2,8 used long echo times (TEs) of 270 ms to optimize lactate and eliminate coresonant lipid signals. However, the use of long TEs has several drawbacks. Signal magnitudes for all peaks are decreased due to T2 relaxation during the long echo interval, and signals from rapidly relaxing compounds, such as lipids and proteins within injured tissue, may disappear entirely. Conclusions-ShortRecently introduced short TE methods can measure both small-molecule peaks from lactate, N-acetyl compounds (NA), creatine, and choline, and macromolecule signals in vivo. 9 We have applied these methods to record changes in the small-molecule and macromolecule spectrum after stroke using single volume techniques. We have also used a 2-dimensional spectroscopic imaging (2D-SI) implementation of these methods to assess the spatial extent and coincidence of the biochemical changes. Subjects and Methods PatientsThis study was reviewed and approved by the Human Investigation Committee of the Yale University School of Medicine. Informed consent was obtained from all subjects before MR examination. A total of 33 single-voxel studies were performed on patients with cortical or deep white matter ischemic strokes identified on a scout image, from which 30 usable spectra were obtained. Twenty-one subjects (11 men and 10 women; average age 64 years, range 38 to 87 years) underwent MRS within 10 days of presentation, and 6 follow-up examinations on days 11,19, 32, 34, 67, and ...

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Lactate production by human monocytes/macrophages determined by proton mr spectroscopy

Cited by 70 publications

References 36 publications

Value of 1H-MRS Using Different Echo Times in Neonates with Cerebral Hypoxia-Ischemia

Value of 1H-MRS Using Different Echo Times in Neonates with Cerebral Hypoxia-Ischemia

Early and Sustained Alterations in Cerebral Metabolism after Traumatic Brain Injury in Immature Rats

Spectroscopic Assessment of Alterations in Macromolecule and Small-Molecule Metabolites in Human Brain After Stroke

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