ABSTRACT
PURPOSE: To investigate how passive hyperthermia affect the resting-state functional brain activity based on an acute mouse model after heat stress exposure. MATERIALS AND METHODS: Twenty-eight rs-fMRI data of C57BL/6J male mice which weighing about 24 â¼ 29 g and aged 12 â¼ 16 weeks were collected. The mice in the hyperthermia group (HT, 40 °C ± 0.5 °C, 40 min) were subjected to passive hyperthermia before the anesthesia preparation for scanning. While the normal control group (NC) was subjected to normothermia condition (NC, 20 °C ± 2 °C, 40 min). After data preprocessing, we performed independent component analysis (ICA) and region of interested (ROI)-ROI functional connectivity (FC) analyses on the data of both HT (n = 13) and NC (n = 15). RESULTS: The group ICA analysis showed that the HT and the NC both included 11 intrinsic connectivity networks (ICNs), and can be divided into four types of networks: the cortical network (CN), the subcortical network (SN), the default mode network (DMN), and cerebellar networks. CN and SN belongs to sensorimotor network. Compared with NC, the functional network organization of ICNs in the HT was altered and the overall functional intensity was decreased. Furthermore, 13 ROIs were selected in CN, SN, and DMN for further ROI-ROI FC analysis. The ROI-ROI FC analysis showed that passive hyperthermia exposure significantly reduced the FC strength in the overall brain represented by CN, SN, DMN of mice. CONCLUSION: Prolonged exposure to high temperature has a greater impact on the overall perception and cognitive level of mice, which might help understand the relationship between neuronal activities and physiological thermal sensation and regulation as well as behavioral changes.
Subject(s)
Brain , Hyperthermia , Mice, Inbred C57BL , Animals , Mice , Male , Brain/physiopathology , Brain/diagnostic imaging , Hyperthermia/physiopathology , Magnetic Resonance Imaging/methodsABSTRACT
Astrocyte-microglial interaction plays a crucial role in brain injury-associated neuroinflammation. Our previous data illustrated that astrocytes secrete microRNA, leading to anti-inflammatory effects on microglia. Long non-coding RNAs participate in neuroinflammation regulation after traumatic brain injury. However, the effect of astrocytes on microglial phenotype via long non-coding RNAs and the underlying molecular mechanisms remain elusive. We used long non-coding RNA sequencing on murine astrocytes and found that exosomal long non-coding RNA 4933431K23Rik attenuated traumatic brain injury-induced microglial activation in vitro and in vivo and ameliorated cognitive function deficiency. Furthermore, microRNA and messenger RNA sequencing together with binding prediction illustrated that exosomal long non-coding RNA 4933431K23Rik up-regulates E2F7 and TFAP2C expression by sponging miR-10a-5p. Additionally, E2F7 and TFAP2C, as transcription factors, regulated microglial Smad7 expression. Using Cx3cr1-Smad7 overexpression of adeno-associated virus, microglia specifically overexpressed Smad7 in the attenuation of neuroinflammation, resulting in less cognitive deficiency after traumatic brain injury. Mechanically, overexpressed Smad7 physically binds to IκBα and inhibits its ubiquitination, preventing NF-κB signaling activation. The Smad7 activator asiaticoside alleviates neuroinflammation and protects neuronal function in traumatic brain injury mice. This study revealed that an exosomal long non-coding RNA from astrocytes attenuates microglial activation after traumatic brain injury by up-regulating Smad7, providing a potential therapeutic target.
Subject(s)
Brain Injuries, Traumatic , MicroRNAs , RNA, Long Noncoding , Mice , Animals , Microglia/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Astrocytes/metabolism , Neuroinflammatory Diseases , MicroRNAs/metabolism , Brain Injuries, Traumatic/genetics , Brain Injuries, Traumatic/metabolism , Phenotype , Mice, Inbred C57BLABSTRACT
Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low molecular weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice. The aim of this consensus paper is to provide an overview and some recommendations on how to handle the MM signals in different types of studies together with a list of open issues in the field, which are all summarized at the end of the paper.
Subject(s)
Brain/diagnostic imaging , Consensus , Expert Testimony , Macromolecular Substances/metabolism , Proton Magnetic Resonance Spectroscopy , Adult , Aged , Aged, 80 and over , Humans , Lipids/chemistry , Magnetic Resonance Imaging , Metabolome , Middle Aged , Models, Theoretical , Signal Processing, Computer-Assisted , Young AdultABSTRACT
Hypoglycemia is critical condition during diabetic treatment that involves intensive insulin therapy, and it may impair brain function. We aimed to compare cortical responses of three hypoglycemic phases and the restoration of glycemia to control levels after a severe episode in rats using non-invasive perfusion magnetic resonance (MR) imaging and localized 1 H MR spectroscopy. Under light α-chloralose anesthesia, cortical blood flow (cCBF) was 42 ± 3 ml/100 g/min at euglycemia (~ 5 mM plasma glucose), was not altered at mild hypoglycemia I (42 ± 4 ml/100 g/min, 2-3.5 mM), increased to 60 ± 8 ml/100 g/min under moderate hypoglycemia II (1-2 mM) and amplified to 190 ± 35 ml/100 g/min at severe hypoglycemia III (< 1 mM). 1 H MRS revealed metabolic changes at hypoglycemia I without any perfusion alteration. At hypoglycemia III, glutamine and glutamate decreased, whereas aspartate increased. When animals subsequently regained glycemic control, not all metabolites returned to their control levels, for example, glutamine. Meanwhile, ascorbate was increased with amplified hypoglycemic severity, whereas glutathione was reduced; these compounds did not return to normal levels upon the restoration of glycemia. Our study is the first to report cCBF and neurochemical changes in cortex upon five glycemic stages. The cortical responses of different hypoglycemic phases would explain variable neuronal damages after hypoglycemia and might help identify the degrees of hypoglycemic insults and further improve alternative therapies.
Subject(s)
Cerebral Cortex/blood supply , Cerebral Cortex/metabolism , Cerebrovascular Circulation/physiology , Hypoglycemia/metabolism , Animals , Cerebral Cortex/physiopathology , Hypoglycemia/physiopathology , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Rats , Rats, Sprague-DawleyABSTRACT
Despite the improving imaging techniques, it remains challenging to produce magnetic resonance (MR) imaging fingerprints depicting severity of acute ischemia. The aim of this study was to evaluate the potential of the overall high-field 1 H MR Spectroscopy (1 H-MRS) neurochemical profile as a metabolic signature for acute ischemia severity in rodent brains. We modeled global ischemia with one-stage 4-vessel-occlusion (4VO) in rats. Vascular structures were assessed immediately by magnetic resonance angiography. The neurochemical responses in the bilateral cortex were measured 1 h after stroke onset by 1 H-MRS. Then we used Partial-Least-Squares discriminant analysis on the overall neurochemical profiles to seek metabolic signatures for ischemic severity subgroups. This approach was further tested on neurochemical profiles of mouse striatum 1 h after permanent middle cerebral artery occlusion, where vascular blood flow was monitored by laser Doppler. Magnetic resonance angiography identified successful 4VO from controls and incomplete global ischemia (e.g., 3VO). 1 H-MR spectra of rat cortex after 4VO showed a specific metabolic pattern, distinct from that of respective controls and rats with 3VO. Partial-Least-Squares discriminant analysis on the overall neurochemical profiles revealed metabolic signatures of acute ischemia that may be extended to mice after permanent middle cerebral artery occlusion. Fingerprinting severity of acute ischemia using neurochemical information may improve MR diagnosis in stroke patients.
Subject(s)
Brain Ischemia/diagnostic imaging , Brain Ischemia/metabolism , Magnetic Resonance Spectroscopy/methods , Peptide Mapping/methods , Severity of Illness Index , Animals , Male , Mice , Mice, Inbred ICR , Protons , Rats , Rats, WistarABSTRACT
Diffusion-weighted 1 H-MRS (DW-MRS) allows for noninvasive investigation of the cellular compartmentalization of cerebral metabolites. DW-MRS applied to the congenital portal systemic shunt (PSS) mouse brain may provide specific insight into alterations of cellular restrictions associated with PSS in humans. At 14.1 T, adult male PSS and their age-matched healthy (Ctrl) mice were studied using DW-MRS covering b-values ranging from 0 to 45 ms/µm2 to determine the diffusion behavior of abundant metabolites. The remarkable sensitivity and spectral resolution, in combination with very high diffusion weighting, allowed for precise measurement of the diffusion properties of endogenous N-acetyl-aspartate, total creatine, myo-inositol, total choline with extension to glutamine and glutamate in mouse brains, in vivo. Most metabolites had comparable diffusion properties in PSS and Ctrl mice, suggesting that intracellular distribution space for these metabolites was not affected in the model. The slightly different diffusivity of the slow decaying component of taurine (0.015 ± 0.003 µm2 /ms in PSS vs 0.021 ± 0.002 µm2 /ms in Ctrl, P < 0.05) might support a cellular redistribution of taurine in the PSS mouse brain.
Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Diffusion Magnetic Resonance Imaging , Metabolome , Portasystemic Shunt, Surgical , Animals , Diffusion , Male , Mice, Inbred C57BL , Monte Carlo Method , Probability , Proton Magnetic Resonance SpectroscopyABSTRACT
We aimed to evaluate the feasibility of neurochemical profiling of embryonic mouse brain developments in utero and to seek potential in vivo evidence of an energy shift in a mitochondrial pyruvate carrier 1 (MPC1) deficient mouse model. C57BL/6 embryonic mouse brains were studied in utero by anatomical MRI and short echo localized proton (1 H) MRS at 14.1 T. Two embryonic stages were studied, the energy shift (e.g., embryonic day 12.5-13, E12.5-13) and close to the birth (E17.5-18). In addition, embryonic brains devoid of MPC1 were studied at E12.5-13. The MRI provided sufficient anatomical contrasts for visualization of embryonic brain. Localized 1 H MRS offered abundant metabolites through the embryonic development from E12.5 and close to the birth, e.g., E17.5 and beyond. The abundant neurochemical information at E12.5 provided metabolic status and processes relating to cellular development at this stage, i.e., the energy shift from glycolysis to oxidative phosphorylation, evidenced by accumulation of lactate in E12.5-13 embryonic brain devoid of MPC1. The further evolution of the neurochemical profile of embryonic brains at E17.5-18 is consistent with cellular and metabolic processes towards the birth. Localized 1 H MRS study of embryonic brain development in utero is feasible, and longitudinal neurochemical profiling of embryonic brains offers valuable insight into early brain development.
Subject(s)
Brain Chemistry , Brain/diagnostic imaging , Brain/embryology , Embryo, Mammalian/metabolism , Proton Magnetic Resonance Spectroscopy , Animals , Feasibility Studies , Female , Male , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
This study demonstrates the suitability of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) for the imaging of congenital portosystemic shunts (PSS) in mice, a vascular abnormality in which mesenteric blood bypasses the liver and is instead drained directly to the systemic circulation. The non-invasive diagnosis performed in tandem with other experimental assessments permits further characterization of liver, whole-body and brain metabolic defects associated with PSS. Magnetic resonance measurements were performed in a 26-cm, horizontal-bore, 14.1-T magnet. MRA was obtained with a three-dimensional gradient echo sequence (GRE; in-plane resolution, 234 × 250 × 234 µm3 ) using a birdcage coil. Two-dimensional GRE MRI with high spatial resolution (in-plane resolution, 100 × 130 µm2 ; slices, 30 × 0.3 mm) was performed using a surface coil. Brain- (dorsal hippocampus) and liver-localized 1 H magnetic resonance spectroscopy (MRS) was also performed with the surface coil. Whole-body metabolic status was evaluated with an oral glucose tolerance test (OGTT). Both MRA and anatomical MRI allowed the identification of hepatic vessels and the diagnosis of PSS in mice. The incidence of PSS was about 10%. Hepatic lipid content was higher in PSS than in control mice (5.1 ± 2.8% versus 1.8 ± 0.6%, p = 0.02). PSS mice had higher brain glutamine concentration than controls (7.3 ± 1.0 µmol/g versus 2.7 ± 0.6 µmol/g, p < 0.0001) and, conversely, lower myo-inositol (4.2 ± 0.6 µmol/g versus 6.0 ± 0.4 µmol/g, p < 0.0001), taurine (9.7 ± 1.2 µmol/g versus 11.0 ± 0.4 µmol/g, p < 0.01) and total choline (0.9 ± 0.1 µmol/g versus 1.2 ± 0.1 µmol/g, p < 0.001) concentrations. Fasting blood glucose and plasma insulin were lower in PSS than in control mice (4.7 ± 0.5mM versus 8.8 ± 0.6mM, p < 0.0001; and 0.04 ± 0.03 µg/L versus 0.3 ± 0.2 µg/L, p = 0.02, respectively). Glucose clearance during OGTT was delayed and less efficient in PSS mice than in controls. Thus, given the non-negligible incidence of PSS in inbred mice, the undiagnosed presence of PSS will, importantly, have an impact on experimental outcomes, notably in studies addressing brain, liver or whole-body metabolism.
Subject(s)
Metabolism , Portasystemic Shunt, Surgical , Animals , Glucose/metabolism , Glucose Tolerance Test , Hippocampus/metabolism , Homeostasis , Liver/diagnostic imaging , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Mice, Inbred C57BLABSTRACT
Ectopic lipid accumulation in the liver is implicated in metabolic disease in an age- and sex-dependent manner. The role of hepatic lipids has been well established within the scope of metabolic insults in mice, but has been insufficiently characterized under standard housing conditions, where age-related metabolic alterations are known to occur. We studied a total of 10 male and 10 female mice longitudinally. At 3, 7 and 11 months of age, non-invasive 1 H-magnetic resonance spectroscopy (1 H-MRS) was used to monitor hepatic lipid content (HLC) and fatty acid composition in vivo, and glucose homeostasis was assessed with glucose and insulin challenges. At the end of the study, hepatic lipids were comprehensively characterized by nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometric analyses of liver tissue samples. In males, HLC increased from 1.4 ± 0.1% at 3 months to 2.9 ± 0.3% at 7 months (p < 0.01) and 2.7 ± 0.3% at 11 months (p < 0.05), in correlation with fasting insulin levels (p < 0.01, r = 0.51) and parameters from the insulin tolerance test (ITT; p < 0.001, r = -0.69 versus area under the curve; p < 0.01, r = -0.57 versus blood glucose drop at 1 h post-ITT; p < 0.01, r = 0.55 versus blood glucose at 3 h post-ITT). The metabolic performance of females remained the same throughout the study, and HLC was higher than that of males at 3 months (2.7 ± 0.2%, p < 0.01), but comparable at 7 months (2.2 ± 0.2%) and 11 months (2.2 ± 0.1%). Strong sexual dimorphism in bioactive lipid species, including diacylglycerols (higher in males, p < 0.0001), phosphatidylinositols (higher in females, p < 0.001) and omega-3 polyunsaturated fatty acids (higher in females, p < 0.01), was found to be in good correlation with metabolic scores at 11 months. Therefore, in mice housed under standard conditions, sex-specific composition of bioactive lipids is associated with metabolic protection in females, whose metabolic performance was independent of hepatic cytosolic lipid content.
Subject(s)
Lipid Metabolism , Liver/metabolism , Sex Characteristics , Aging/metabolism , Animals , Body Weight , Female , Hormones/metabolism , Male , Metabolome , Mice, Inbred C57BL , Pancreas/metabolism , Proton Magnetic Resonance SpectroscopyABSTRACT
In the brain, glycogen is a source of glucose not only in emergency situations but also during normal brain activity. Altered brain glycogen metabolism is associated with energetic dysregulation in pathological conditions, such as diabetes or epilepsy. Both in humans and animals, brain glycogen levels have been assessed non-invasively by Carbon-13 Magnetic Resonance Spectroscopy (13C-MRS) in vivo. With this approach, glycogen synthesis and degradation may be followed in real time, thereby providing valuable insights into brain glycogen dynamics. However, compared to the liver and muscle, where glycogen is abundant, the sensitivity for detection of brain glycogen by 13C-MRS is inherently low. In this review we focus on strategies used to optimize the sensitivity for 13C-MRS detection of glycogen. Namely, we explore several technical perspectives, such as magnetic field strength, field homogeneity, coil design, decoupling, and localization methods. Furthermore, we also address basic principles underlying the use of 13C-labeled precursors to enhance the detectable glycogen signal, emphasizing specific experimental aspects relevant for obtaining kinetic information on brain glycogen.
Subject(s)
Brain/metabolism , Carbon Isotopes/metabolism , Glycogen/metabolism , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Animals , Humans , Models, BiologicalABSTRACT
BACKGROUND: The heart relies on continuous energy production and imbalances herein impair cardiac function directly. The tricarboxylic acid (TCA) cycle is the primary means of energy generation in the healthy myocardium, but direct noninvasive quantification of metabolic fluxes is challenging due to the low concentration of most metabolites. Hyperpolarized (13)C magnetic resonance spectroscopy (MRS) provides the opportunity to measure cellular metabolism in real time in vivo. The aim of this work was to noninvasively measure myocardial TCA cycle flux (VTCA) in vivo within a single minute. METHODS AND RESULTS: Hyperpolarized [1-(13)C]acetate was administered at different concentrations in healthy rats. (13)C incorporation into [1-(13)C]acetylcarnitine and the TCA cycle intermediate [5-(13)C]citrate was dynamically detected in vivo with a time resolution of 3s. Different kinetic models were established and evaluated to determine the metabolic fluxes by simultaneously fitting the evolution of the (13)C labeling in acetate, acetylcarnitine, and citrate. VTCA was estimated to be 6.7±1.7 µmol·g(-1)·min(-1) (dry weight), and was best estimated with a model using only the labeling in citrate and acetylcarnitine, independent of the precursor. The TCA cycle rate was not linear with the citrate-to-acetate metabolite ratio, and could thus not be quantified using a ratiometric approach. The (13)C signal evolution of citrate, i.e. citrate formation was independent of the amount of injected acetate, while the (13)C signal evolution of acetylcarnitine revealed a dose dependency with the injected acetate. The (13)C labeling of citrate did not correlate to that of acetylcarnitine, leading to the hypothesis that acetylcarnitine formation is not an indication of mitochondrial TCA cycle activity in the heart. CONCLUSIONS: Hyperpolarized [1-(13)C]acetate is a metabolic probe independent of pyruvate dehydrogenase (PDH) activity. It allows the direct estimation of VTCA in vivo, which was shown to be neither dependent on the administered acetate dose nor on the (13)C labeling of acetylcarnitine. Dynamic (13)C MRS coupled to the injection of hyperpolarized [1-(13)C]acetate can enable the measurement of metabolic changes during impaired heart function.
Subject(s)
Citric Acid Cycle , Magnetic Resonance Imaging , Myocardium/metabolism , Tricarboxylic Acids/metabolism , Acetylcarnitine , Animals , Carbon Isotopes/administration & dosage , Humans , Mitochondria, Heart/metabolism , Mitochondria, Heart/pathology , Myocardium/pathology , Rats , Tricarboxylic Acids/isolation & purificationABSTRACT
Alterations in the hepatic lipid content (HLC) and fatty acid composition are associated with disruptions in whole body metabolism, both in humans and in rodent models, and can be non-invasively assessed by (1)H-MRS in vivo. We used (1)H-MRS to characterize the hepatic fatty-acyl chains of healthy mice and to follow changes caused by streptozotocin (STZ) injection. Using STEAM at 14.1 T with an ultra-short TE of 2.8 ms, confounding effects from T2 relaxation and J-coupling were avoided, allowing for accurate estimations of the contribution of unsaturated (UFA), saturated (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA) fatty-acyl chains, number of double bonds, PU bonds and mean chain length. Compared with in vivo (1) H-MRS, high resolution NMR performed in vitro in hepatic lipid extracts reported longer fatty-acyl chains (18 versus 15 carbons) with a lower contribution from UFA (61 ± 1% versus 80 ± 5%) but a higher number of PU bonds per UFA (1.39 ± 0.03 versus 0.58 ± 0.08), driven by the presence of membrane species in the extracts. STZ injection caused a decrease of HLC (from 1.7 ± 0.3% to 0.7 ± 0.1%), an increase in the contribution of SFA (from 21 ± 2% to 45 ± 6%) and a reduction of the mean length (from 15 to 13 carbons) of cytosolic fatty-acyl chains. In addition, SFAs were also likely to have increased in membrane lipids of STZ-induced diabetic mice, along with a decrease of the mean chain length. These studies show the applicability of (1)H-MRS in vivo to monitor changes in the composition of the hepatic fatty-acyl chains in mice even when they exhibit reduced HLC, pointing to the value of this methodology to evaluate lipid-lowering interventions in the scope of metabolic disorders.
Subject(s)
Adipose Tissue/metabolism , Diabetes Mellitus, Experimental/metabolism , Fatty Acids/metabolism , Liver/metabolism , Proton Magnetic Resonance Spectroscopy/methods , Adiposity , Animals , Biomarkers/metabolism , Diabetes Mellitus, Experimental/chemically induced , Mice , Mice, Inbred C57BL , Reproducibility of Results , Sensitivity and Specificity , Streptozocin , Tissue DistributionABSTRACT
Although numerous positron emission tomography (PET) studies with (18) F-fluoro-deoxyglucose (FDG) have reported quantitative results on cerebral glucose kinetics and consumption, there is a large variation between the absolute values found in the literature. One of the underlying causes is the inconsistent use of the lumped constants (LCs), the derivation of which is often based on multiple assumptions that render absolute numbers imprecise and errors hard to quantify. We combined a kinetic FDG-PET study with magnetic resonance spectroscopic imaging (MRSI) of glucose dynamics in Sprague-Dawley rats to obtain a more comprehensive view of brain glucose kinetics and determine a reliable value for the LC under isoflurane anaesthesia. Maps of Tmax /CMRglc derived from MRSI data and Tmax determined from PET kinetic modelling allowed to obtain an LC-independent CMRglc . The LC was estimated to range from 0.33 ± 0.07 in retrosplenial cortex to 0.44 ± 0.05 in hippocampus, yielding CMRglc between 62 ± 14 and 54 ± 11 µmol/min/100 g, respectively. These newly determined LCs for four distinct areas in the rat brain under isoflurane anaesthesia provide means of comparing the growing amount of FDG-PET data available from translational studies.
Subject(s)
Algorithms , Anesthetics, Inhalation/pharmacology , Brain Chemistry/drug effects , Brain/metabolism , Glucose/metabolism , Isoflurane/pharmacology , Magnetic Resonance Spectroscopy/methods , Multimodal Imaging/methods , Positron-Emission Tomography/methods , Animals , Biological Transport , Brain/diagnostic imaging , Brain/drug effects , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Fluorine Radioisotopes/analysis , Fluorine Radioisotopes/pharmacokinetics , Fluorodeoxyglucose F18/analysis , Fluorodeoxyglucose F18/pharmacokinetics , Hippocampus/diagnostic imaging , Hippocampus/drug effects , Hippocampus/metabolism , Models, Biological , Radiopharmaceuticals/analysis , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Sprague-Dawley , Thalamus/diagnostic imaging , Thalamus/drug effects , Thalamus/metabolismABSTRACT
Total adenosine triphosphate (tATP) was investigated for its potential as a rapid indicator of cyanobacterial growth and algaecide effectiveness. tATP and other common bloom monitoring parameters were measured over the growth cycles of cyanobacteria and green algae in laboratory cultures and examined at a drinking water source during an active bloom. Strong correlations (R2>0.78) were observed between tATP and chlorophyll-a in cyanobacteria cultures. tATP offered greater sensitivity by increasing two orders of magnitude approximately 7 d before changes in chlorophyll-a or optical density were observed in Lyngbya sp. and Dolichospermum sp. cultures. Increases in tATP per cell coincided with the onset of exponential growth phases in lab cultures and increase in cell abundance in field samples, suggesting that ATP/cell is a sensitive indicator that may be used to identify the development of blooms. Bench-scale trials using samples harvested during a bloom showed that tATP exhibited a clear dose-response during copper sulfate (CuSO4) and hydrogen peroxide (H2O2) treatment compared to chlorophyll-a and cell counts, indicating that cellular production and storage of ATP decreases even when live and dead cells cannot be distinguished. During Copper (Cu) algaecide application at a reservoir used as a drinking water source, tATP and cell counts decreased following initial algaecide application; however, the bloom rebounded within 10 d showing that the Cu algaecide only has limited effectiveness. In this case, tATP was a sensitive indicator to bloom rebounding after algaecide treatments and correlated positively with cell counts (R2=0.7). These results support the use of tATP as a valuable complementary bloom monitoring tool for drinking water utilities to implement during the monitoring and treatment of cyanobacterial blooms.
Subject(s)
Glucose/metabolism , Hypothalamus/diagnostic imaging , Hypothalamus/metabolism , Magnetic Resonance Spectroscopy , Animals , Feasibility Studies , Lactic Acid/metabolism , Male , Mice , Mice, Inbred C57BL , Models, Theoretical , Phantoms, Imaging , Protons , Radio Waves , Signal-To-Noise Ratio , Spectrophotometry , Surface PropertiesABSTRACT
Biochar is preferentially recommended for the remediation of heavy metal-polluted soils. Sunflower is an important high-biomass oil crop with a promising potential for phytoremediation of Cr(VI)-polluted soil. However, how biochar affects sunflower growth and Cr accumulation in Cr(VI)-polluted soil needs to be elucidated. Here, a pot culture experiment was conducted to study whether soil amendment with biochar (0, 0.1%, 1%, and 5%, w/w) can mitigate Cr toxicity and accumulation in sunflower seedlings grown in soils artificially polluted with different levels of Cr(VI) (0, 50, and 250 mg Cr(VI)/kg soil). The addition of Cr(VI) exhibited significant phytotoxicity, as evidenced by inhibited plant growth and even the death of seedlings at 250 mg/kg Cr(VI). Overall, biochar amendment showed positive effects on plant growth and Cr immobilization, dependent on both the biochar dose and Cr addition level. When 50 mg/kg Cr(VI) was added, 1% biochar showed positive effects similar to 5% biochar on improving plant growth and mineral nutrition (particularly K), reducing Cr content in shoots and roots, and decreasing Cr availability and Cr(VI) content in the soil. In comparison with non-amendment, 1% and 5% biochar caused 85% and 100% increase in shoot dry weights, and 75% and 86% reduction in shoot Cr concentrations, respectively. When 250 mg/kg Cr(VI) was added, a 5% dose produced much better benefits than 1%, while a 0.1% dose did not help plants to survive. Overall, an appropriate dose of biochar enhanced Cr(VI) immobilization and subsequently decreased its toxicity and accumulation in sunflower seedlings. Our findings confirm that biochar can be used as an efficient amendment for the remediation of Cr(VI)-polluted soils and cleaner production of sunflower oil and biomass.
ABSTRACT
Proton NMR spectroscopy is emerging from translational and preclinical neuroscience research as an important tool for evidence based diagnosis and therapy monitoring. It provides biomarkers that offer fingerprints of neurological disorders even in cases where a lesion is not yet observed in MR images. The collection of molecules used as cerebral biomarkers that are detectable by (1)H NMR spectroscopy define the so-called "neurochemical profile". The non-invasive quality of this technique makes it suitable not only for diagnostic purposes but also for therapy monitoring paralleling an eventual neuroprotection. The application of (1)H NMR spectroscopy in basic and translational neuroscience research is discussed here.
Subject(s)
Brain Chemistry , Magnetic Resonance Spectroscopy/methods , Animals , Blood-Brain Barrier/anatomy & histology , Blood-Brain Barrier/physiology , Brain/physiology , Brain/physiopathology , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Proliferation , Electromagnetic Fields , Humans , Magnetic Resonance Spectroscopy/instrumentation , Membrane Lipids/metabolism , Nervous System Diseases/diagnosis , Neurotransmitter Agents/metabolism , Species Specificity , Translational Research, BiomedicalABSTRACT
After ischemic stroke, the ischemic damage to brain tissue evolves over time and with an uneven spatial distribution. Early irreversible changes occur in the ischemic core, whereas, in the penumbra, which receives more collateral blood flow, the damage is more mild and delayed. A better characterization of the penumbra, irreversibly damaged and healthy tissues is needed to understand the mechanisms involved in tissue death. MRSI is a powerful tool for this task if the scan time can be decreased whilst maintaining high sensitivity. Therefore, we made improvements to a (1)H MRSI protocol to study middle cerebral artery occlusion in mice. The spatial distribution of changes in the neurochemical profile was investigated, with an effective spatial resolution of 1.4 µL, applying the protocol on a 14.1-T magnet. The acquired maps included the difficult-to-separate glutamate and glutamine resonances and, to our knowledge, the first mapping of metabolites γ-aminobutyric acid and glutathione in vivo, within a metabolite measurement time of 45 min. The maps were in excellent agreement with findings from single-voxel spectroscopy and offer spatial information at a scan time acceptable for most animal models. The metabolites measured differed with respect to the temporal evolution of their concentrations and the localization of these changes. Specifically, lactate and N-acetylaspartate concentration changes largely overlapped with the T(2)-hyperintense region visualized with MRI, whereas changes in cholines and glutathione affected the entire middle cerebral artery territory. Glutamine maps showed elevated levels in the ischemic striatum until 8 h after reperfusion, and until 24 h in cortical tissue, indicating differences in excitotoxic effects and secondary energy failure in these tissue types.
Subject(s)
Brain Ischemia/metabolism , Magnetic Resonance Spectroscopy/methods , Animals , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Brain Ischemia/complications , Brain Ischemia/pathology , Glutamic Acid/metabolism , Glutathione/metabolism , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/pathology , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/metabolism , Ischemic Attack, Transient/pathology , Lactic Acid/metabolism , Male , Mice , Mice, Inbred ICR , Models, Biological , Neostriatum/metabolism , Neurochemistry , Taurine/metabolism , Time Factors , gamma-Aminobutyric Acid/metabolismABSTRACT
BACKGROUND AND PURPOSE: Despite the improving imaging techniques, it remains challenging to predict the outcome early after transient cerebral ischemia. The aim of this study was thus to identify early metabolic biomarkers for outcome prediction. METHODS: We modeled transient ischemic attacks and strokes in mice. Using high-field MR spectroscopy, we correlated early changes in the neurochemical profile of the ischemic striatum with histopathologic alterations at a later time point. RESULTS: A significant increase in glutamine was measured between 3 hours and 8 hours after all ischemic events followed by reperfusion independently of the outcome and can thus be considered as an indicator of recent transient ischemia. On the other hand, a reduction of the score obtained by summing the concentrations of N-acetyl aspartate, glutamate, and taurine was a good predictor of an irreversible lesion as early as 3 hours after ischemia. CONCLUSIONS: We identified biomarkers of reversible and irreversible ischemic damage, which can be used in an early predictive evaluation of stroke outcome.
Subject(s)
Aspartic Acid/analogs & derivatives , Glutamine/metabolism , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/metabolism , Taurine/metabolism , Animals , Aspartic Acid/metabolism , Biomarkers/metabolism , Disease Models, Animal , Magnetic Resonance Spectroscopy/methods , Male , Mice , Mice, Inbred ICR , Predictive Value of Tests , Time FactorsABSTRACT
Glucose is a major energy fuel for the brain, however, less is known about specificities of its metabolism in distinct cerebral areas. Here we examined the regional differences in glucose utilization between the hypothalamus and hippocampus using in vivo indirect 13C magnetic resonance spectroscopy (1H-[13C]-MRS) upon infusion of [1,6-13C2]glucose. Using a metabolic flux analysis with a 1-compartment mathematical model of brain metabolism, we report that compared to hippocampus, hypothalamus shows higher levels of aerobic glycolysis associated with a marked gamma-aminobutyric acid-ergic (GABAergic) and astrocytic metabolic dependence. In addition, our analysis suggests a higher rate of ATP production in hypothalamus that is accompanied by an excess of cytosolic nicotinamide adenine dinucleotide (NADH) production that does not fuel mitochondria via the malate-aspartate shuttle (MAS). In conclusion, our results reveal significant metabolic differences, which might be attributable to respective cell populations or functional features of both structures.