Imbalance of thalamic metabolites in an experimental model of hypertension: role of bergamot polyphenols.

Cerebral metabolites are associated with different physiological and pathological processes in brain tissue. Among them, the concentrations of N-acetylaspartate (NAA) and choline-containing compounds (Cho) in the thalamic region are recognized and analyzed as important predictive markers of brain impairment. The relationship among hypertension, modulation of brain metabolite levels and cerebral diseases is of recent investigation, leaving many unanswered questions regarding the origin and consequences of the metabolic damage caused in grey and white matter during hypertension. Here we provide evidence for the influence of hypertension on NAA and Cho ratios in hypertensive rat thalamus and how the use of natural occurring compounds ameliorates the balance of thalamic metabolites.

Circulating Cytokines Predict 1H-Proton MRS Cerebral Metabolites in Healthy Older Adults.

Background: Changes in both circulating cytokines and neurochemical concentrations have been observed in aging. Patterns of change across these factors are associated with age-related pathologies, including neurodegenerative disease. More evidence to define patterns of change that are characteristic of healthy aging is needed, as is an investigation into how age-related changes in blood cytokines and brain neurochemicals may relate to one another in a healthy older adult population. Methods: Single voxel 1H-proton magnetic resonance spectroscopy was collected in medial frontal and medial parietal regions. Phosphocholine and glycerophosphocholine (Cho), myo-inositol (MI), N-acetylaspertate and N-acetylasperglutamate (NAA), creatine and phosphocreatine (Cr), and glutamate and glutamine (Glx) were measured in a sample of 83 healthy, cognitively normal adults aged 52-89. Blood data were collected to quantify 12 cytokines: interleukins (IL-) 2, 5, 6, 7, 8, 10, 12, 13, IL-1 ß, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and IL-17 α. Correlation analyses were performed to assess age relationships between each of these factors. Backward linear regressions were performed. Cytokine data and age were used as predictors of each cerebrospinal fluid (CSF)-corrected metabolite concentration in both voxels. Results: Associations were identified between a variety of cytokines and concentrations of frontal NAA, Cr, and Glx, and of parietal MI, Cho, NAA, and Cr. In the frontal voxel, NAA was predicted by more IL-1B and less TNF-α, Cr by less TNF-α and more IL-5, and Glx by less TNF-α. In the parietal voxel, MI was predicted by more IL-10 and IL-8 and less IL-2, Cho by more TNF-α and less IL-2, NAA by more IL-1B and TNF-α and less IL-13, IL-2, and IL-7, and Cr by more IL-10 and less IL-2. Conclusions: Associations were identified between circulating cytokines and neurometabolite concentrations in this sample of older adults. The present results serve as the initial evidence of relationships between circulating cytokines and neurophysiology. Findings invite further investigation to understand the physiological consequences of aging, and how peripheral inflammatory markers may relate to neurochemical concentrations in healthy aging.

Serial Cerebral Metabolic Changes in Patients With Ischemic Stroke Treated With Autologous Bone Marrow Derived Mononuclear Cells.

Purpose: Cell-based therapy offers new opportunities for the development of novel treatments to promote tissue repair, functional restoration, and cerebral metabolic balance. N-acetylasperate (NAA), Choline (Cho), and Creatine (Cr) are three major metabolites seen on proton magnetic resonance spectroscopy (MRS) that play a vital role in balancing the biochemical processes and are suggested as markers of recovery. In this preliminary study, we serially monitored changes in these metabolites in ischemic stroke patients who were treated with autologous bone marrow-derived mononuclear cells (MNCs) using non-invasive MRS. Materials and Methods: A sub-group of nine patients (3 male, 6 female) participated in a serial MRS study, as part of a clinical trial on autologous bone marrow cell therapy in acute ischemic stroke. Seven to ten million mononuclear cells were isolated from the patient's bone marrow and administered intravenously within 72 h of onset of injury. MRS data were obtained at 1, 3, and 6 months using a whole-body 3.0T MRI. Single voxel point-resolved spectroscopy (PRESS) was obtained within the lesion and contralesional gray matter. Spectral analysis was done using TARQUIN software and absolute concentration of NAA, Cho, and Cr was determined. National Institute of Health Stroke Scale (NIHSS) was serially recoreded. Two-way analysis of variance was performed and p < 0.05 considered statistically significant. Results: All metabolites showed statistically significant or clear trends toward lower ipsilesional concentrations compared to the contralesional side at all time points. Statistically significant reductions were found in ipsilesional NAA at 1M and 3M, Cho at 6M, and Cr at 1M and 6M (p < 0.03), compared to the contralesional side. Temporally, ipsilesional NAA increased between 3M and 6M (p < 0.01). On the other hand, ipsilesional Cho showed continued decline till 6M (p < 0.01). Ipsilesional Cr was stable over time. Contralesional metabolites were relatively stable over time, with only Cr showing a reduction 3M (p < 0.02). There was a significant (p < 0.03) correlation between ipsilesional NAA and NIHSS at 3M follow-up. Conclusion: Serial changes in metabolites suggest that MRS can be applied to monitor therapeutic changes. Post-treatment increasing trends of NAA concentration and significant correlation with NIHSS support a potential therapeutic effect.

Repeatability of two-dimensional chemical shift imaging multivoxel proton magnetic resonance spectroscopy for measuring human cerebral choline-containing compounds.

AIM: To investigate the repeatability of proton magnetic resonance spectroscopy in the in vivo measurement of human cerebral levels of choline-containing compounds (Cho). METHODS: Two consecutive scans were carried out in six healthy resting subjects at a magnetic field strength of 1.5 T. On each occasion, neurospectroscopy data were collected from 64 voxels using the same 2D chemical shift imaging (CSI) sequence. The data were analyzed in the same way, using the same software, to obtain the values for each voxel of the ratio of Cho to creatine. The Wilcoxon related-samples signed-rank test, coefficient of variation (CV), repeatability coefficient (RC), and intraclass correlation coefficient (ICC) were used to assess the repeatability. RESULTS: The CV ranged from 2.75% to 33.99%, while the minimum RC was 5.68%. There was excellent reproducibility, as judged by significant ICC values, in 26 voxels. Just three voxels showed significant differences according to the Wilcoxon related-samples signed-rank test. CONCLUSION: It is therefore concluded that when CSI multivoxel proton neurospectroscopy is used to measure cerebral choline-containing compounds at 1.5 T, the reproducibility is highly acceptable.

Dynamic MR Spectroscopy of brain metabolism using a non-conventional spectral averaging scheme.

PURPOSE: MRS acquisition based on the blood oxygenation level dependent (BOLD) contrast mechanism was implemented at 3T to investigate the impact of a non-conventional spectral averaging scheme (determined by the number of RF excitations, NEX) on the dynamics of cerebral metabolism during neuroactivation. Using NEX=2, water and metabolite BOLD responses were compared to previous results from standard experiments. METHODS: Spectra were recorded from the visual cortex of five healthy volunteers during single and block visual stimulations. The height, width and area of the spectral peaks were calculated (using SAGE v7) in order to estimate their percentage changes from baseline (representing the BOLD change) following visual stimulation. BOLD changes were statistically significant at a significance level of p<0.05 by paired t-test. RESULTS: Significantly greater BOLD changes in all spectra were observed in the single than block stimulation (p<0.05). The water resonance showed significant (p<0.01) BOLD changes in all peak parameters in both paradigms. All metabolites showed significant increase in spectral height (p<0.01) in the single paradigm, but none of them (except the height of Cho) showed significant BOLD response in the block paradigm. BOLD changes observed in the block paradigm were generally lower than reported changes. CONCLUSIONS: The time interval of 6s offered by NEX=2 during which each line of spectral data is recorded by the scanner is rather long, leading to some BOLD data loss particularly in a block experimental design.

Application of 9.4 T 1 H-MR spectroscopy in determination of lactate in brain of mice with early acute hypoxia-ischeia injury and its significance / 吉林大学学报(医学版)

Objective:To explore the lactate metabolism in brain tissue of the mice with early acute hypoxia-ischemia injury,and to provide data support for 9.4T 1 H-NMR spectroscopy in detecting the lactate level clinically.Methods:Eighty Kunming mice were randomly divided into sixteen groups (0 s,20 s,40 s,60 s,2 min,4 min, 6 min,8 min, 10 min, 12 min, 14 min, 16 min, 18 min,and 20 min)according to the duration of hypoxia-ischemia (n=5).The changes of lactate levels were detected by 9.4T 1 H-NMR spectroscopy. Results:After the initiation of hypoxia-ischemia injury,the lactate level began to increase rapidly to the highest value of (6.89 ± 0.34)μmol·g-1 at 20 s,then started to decline quickly from 40 s to 2 min,and eventually decreased to a stable level of (4.85±0.36)μmol·g-1 until 6 min.Compared with control group,the levels of lactate in brain tissue of the mice in hypoxic-ischemic groups were increased (P <0.01).Conclusion:40 s of acute hypoxia-ischemia may be the lactate cerebral neuron threshold during the anaerobic glycolysis. 9.4T1 H-MRS can provide the exact time window for detecting the lactate metabolism.