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In the carboxylic/amide region, brain ¹³C signals can only have one one-bond ¹³C-¹³C homonuclear coupling. As such only doublets (with a ¹³C-¹³C coupling of ~50 Hz) and singlets exist in this region. The large one-bond ¹³C-¹³C J coupling and the lack of interference from other isotopomers provide a unique condition for simultaneous detection of metabolism of different substrates. Examples of co-infusion of [¹³C₆]-D-glucose and [1-¹³C] acetate as well as co-infusion of [¹³C₆]-D-glucose and [1,3-¹³C₂] hydroxybutyrate are shown to demonstrate in vivo simultaneous detection of different metabolic pathways in the brain using ¹³C MRS of the carboxylic/amide region.

Acetate is a glia-specific subtract and has been used to study brain metabolism. Potential risk in intravenously infusing sodium acetate to patients is unknown in many disorders. The effect of alcohol (ethanol) consumption is well understood. Alcohol is predominantly metabolized into acetate in the liver. In the present study, steady sate ¹³C spectra of rat brain acquired after administration of [1-¹³C] ethanol were found to be highly similar to spectra obtained using [1-¹³C] acetate, suggesting that oral administration of [1-¹³C] alcohol could replace intravenous infusion of sodium [1-¹³C] acetate in certain studies when the direct effect of alcohol is unimportant for the subject of the study.

The rat lateral septum has been shown to be involved in the expression of anxiety-behaviors such as those involved in conflict procedures. The neurochemical profile of the lateral septum has however never been characterized using proton magnetic resonance spectroscopy in the rat. In the present work, the neurochemical profile of the rat lateral septum was measured at 9.4T using 1H-MRS demonstrating significant changes compared to similar data measured in unspecific rat brain regions. It appears essential to characterize the metabolic profile of specific brain areas with accuracy using 1H MRS.

Parkisnon's disease, 1H MRS, Glutamte, Glutamine, GABA, nucleus accumbens

Knowledge of neurotransmitter metabolism is very important for understanding the pathophysiology of neurological disorders. In the present study we have investigated neuronal TCA cycle and neurotransmitter cycle flux in different brain regions of C57BL6 mouse. Mice were infused with [1,6-¹³C₂]glucose for different time ranging from 7 to 90 min or [2-¹³C]acetate for ~90 min. Brain metabolite levels and ¹³C labeling of amino acids were measured with ¹H-[¹³C]-NMR spectroscopy at 14T NMR spectrometer. The metabolite levels were distinct in different regions of the brain. Glutamatergic rate was higher in cortex while GABAergic was more in cerebellum and olfactory bulb.

This study was to characterize the regional neurochemical profiles of canine brain using NMRS, tissue extraction, and external simulated phantom concentration quantification. The occipital, frontal, and temporal lobes, thalami, cerebellar cortices, and spinal cords of adult beagles were obtained, and NMR samples were prepared using M/C extraction method. The metabolite concentrations in canine brain tissues were measured and compared with those found in human and rat brain. In addition, the cross peaks of brain metabolites were identified using 2D-COSY. This study demonstrated the absolute quantification of canine neuronal parts using MRS, with tissue extraction used to measure metabolite concentrations.

The ketamine, a NMDA receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms similar to schizophrenia. In this study, we used in vivo and in vitro 1H-NMR spectroscopy to examine the brain metabolism of rat treated with subanesthetic dose of ketamine. In vivo data for Glu/Gln abnormalities in ketamine-treated rats may support the hypotheses of glutamate dysfunction for schizophrenia. In addition lower metabolic level of NAA in rats treated with ketamine may indicate reduced neuronal viability. Therefore our findings suggest that the neurochemical alterations induced by ketamine may provide the foundation for pathophysiological models of schizophrenia.

An in vitro proton MRS study was carried out on mice ranging from 3 to 18 months in order to investigate cerebral metabolic differences between TASTPM Alzheimer's mice and their wild type base strain. An effect of genotype was observed for myo-inositol, with concentration being higher in TASTPM mice, myo-inositol may therefore be an Alzheimer's marker. Lower levels of succinate were observed in TASTPM mice, being an effect of both age and genotype. This may indicate impaired neuronal energy production or mitochondrial dysfunction. The results also call into question the use of creatine as a reference metabolite.

Understanding hypoglycemia became very essential for treating diabetes in clinical. We explored ¹H MR studies, including cerebral blood flow and neurochemical profile of cortical tissue under insulin-induced hypoglycemia in rats.

The prematurely ageing mtDNA mutator mouse was used to study mitochondrial dysfunction in the brain. ¹H-MRS detected a 2-fold increase in cortical and striatal lactate levels as early as 6-9 weeks and continued throughout the lives of mtDNA mutator mice (average life span 45-48 weeks). Increased brain lactate levels were confirmed postmortem by high-performance liquid chromatography (HPLC). These methods revealed that abnormally high lactate levels in the CNS are an early phenotype of premature ageing in the mtDNA mutator mouse. Our data support the hypothesis of abnormal metabolism in ageing due to mitochondrial dysfunction.

Mouse brain structural and metabolic stability were determined by T₁ and T₂ mapping and DTI at 0.7 and 0.9 s of 4 kW FBMI and by quantitative single voxel PRESS, respectively. Measures were taken in-vivo before and repetitively, at 1.17 hour intervals, after FBMI. Analysis continued for a total duration of 16 hours at room temperature. The longer FBMI duration was best for maintaining metabolite levels in the mouse brain; whereas T₁, T₂, and DTI metrics were best maintained by shorter duration FBMI.

Phosphoethanolamine concentration ([PE]) is high in neonatal brain. [PE] reduction increases mitochondrial respiration. We aimed to elucidate PE's metabolic role following hypoxia-ischaemia (HI). Thirty-three piglets were studied by 31P MRS (27 HI; 6 controls). For severe cerebral injury [PE]/[exchangeable phosphate pool] fell below controls but later recovered: however, [PE]/[nucleotide triphosphate (NTP; mainly ATP)] was almost constant suggesting strong PE to NTP coupling. In cells stressed after HI reduced [ATP] may inhibit ethanolamine phosphokinase resulting in [PE] reduction and stimulation of ATP generation by surviving mitochondria. High neonatal [PE] may be a factor evolved to counter mammalian cerebral birth trauma.

Hepatic Encephalopathy is associated with hyperammonemia and energetic changes in brain. In animal models and patients with mild HE, L-carnitine has been shown to be protective. In order to investigate the effect of L-carnitine on brain energy-metabolism, multinuclear NMR was used to measure metabolic pathways in brain following administration of [U-13C]glucose in ammonia-treated rats with PCA. In ammonia-precipitated encephalopathy, L-carnitine considerably delayed the time to coma, concomitantly to enhanced ammonia detoxification via astrocytic glutamine synthesis and attenuation of lactate accumulation. These results indicate to cell-specific actions of L-carnitine which might explain its therapeutic effect in ammonia-precipitated HE in cirrhotic patients.

Until recently, no data are available about the behavioral and simultaneous non-invasive measurements of neurochemial responses following antidepressant treatment in mice FST model. In this study, in vivo 1H-MRS at 9.4 T was used to examine the effects of desipramine (DMI) pretreatment on behavioral and regional neurocheimal responses of C57BL/6 mice brain. We found significant behavioral changes as well as metabolic alterations of glutamate and myo-inositol by the DMI pretreatment. Our results suggest that glutamatergic activity and glial cell dysfunction contribute to pathophysiological mechanisms underlying depression and that modulation of synaptic neurotransmitter concentrations represent invaluable targets for antidepressant drug development.

Animal models for depression are indispensable tools in the search to identify new antidepressant drugs. The forced swimming test (FST) is the most widely used tool for assessing antidepressant activity in rodents. Few studies have been performed proton spectroscopy to assess antidepressant effects on brain metabolism of rat exposed to the FST. The in vivo proton spectra quantified by LCModel revealed that myo-inositol metabolic level in left dorsolateral prefrontal cortex of rat was significantly altered in both FST and desipramine treated group. Our findings suggest a possible role of myo-inositol within the left DLPFC of rat model for depression.

In vivo ¹H NMR NMR spectroscopy at 9.4T was used to investigate effects of morphine on the neurochemical profile of the developing rat hippocampus. Significant differences between pup exposed to the morphine (2 mg/kg/, twice a day, P3 – P7) and their littermate controls were observed for multiple brain metabolites on postnatal day 8. These changes had resolved by P29. Biochemical changes indicated effects of morphine on inhibitory neurotransmission (GABA, Tau), glial development and myelination (Gln, myo-Ins), osmoregulation (myo-Ins, Tau) and antioxidant processes (GSH).These results indicate that morphine exposure during hippocampal development may lead to hippocampal-dependant cognitive deficits in premature infants.

N-acetylaspartate (NAA), a metabolite synthesized in neuronal mitochondria and detected by proton magnetic resonance spectroscopy (MRS), might serve as a non-invasive biomarker of mitochondrial integrity after traumatic brain injury (TBI). Previous studies in human survivors of TBI have linked NAA with cognitive recovery, although the specific mechanism has not been elucidated. We have examined a time course of changes in NAA and behavioral impairment after TBI in a well-characterized animal model. We then investigated whether these NAA changes are sensitive to manipulation of mitochondrial status by cyclosporine A (CsA), an experimental neuroprotective agent that inhibits mitochondrial permeability transition after TBI.

Repetitive iatrogenic hypoglycemic events lead to brain adaptations resulting in failing counterregulatory response and lack of warning symptoms (hypoglycemia unawareness) normally associated with low blood glucose levels. Increased blood-brain barrier lactate transport via upregulated monocarboxylic acid transporter 1 (MCT1) has been suggested as an adaptation induced by repetitive hypoglycemia. Increased lactate uptake and oxidation could (partially) replace glucose thereby contribute to hypoglycemia unawareness and failing counterregulatory response. We used ¹H-[¹³C] MRS combined with [3-¹³C]-lactate infusion during hypoglycemia to investigate the role of increased lactate transport and/or metabolism in the brain of a rat model with ketogenic diet-induced upregulation of MCT1.

Neurotransmitter levels of glutamate and glutamine are tightly coupled with modulation of one resulting in a corresponding opposing change in the other. Since glutamate is implicated in a variety of neurological disorders, the observation of an endogenous pool of glutamate (Glu) and glutamine (Gln) and/or its ratio can serve as a strong mechanistic biomarker and measure of efficacy. Flupirtine, a potassium channel opener, has been shown to cause decrease in Glu and a relative increase in Gln in the rat hippocampus.

Out of a group of 17 animals eight were made dependent by 7 weeks ethanol vapor exposure with peak levels up to 4 g/l blood alcohol concentration. We assessed metabolic profiles in two brain regions with functional importance for dependence, i.e. medial prefrontal cortex and hippocampus, using in vivo single-voxel 1H magnetic resonance spectroscopy at TE=10 ms on a 9.4T scanner. Animals were measured up to 5 times before during and after ethanol exposure. Reduced myoinositol and N-acetylaspartate levels as well as increased choline-containing compounds were found during intoxication. Raised glutamate levels were found during early withdrawal.

The present study examined the effects of sleep fragmentation (SF) in the hippocampus and the cortex of mice using proton MR spectroscopy at 14.1T. Disruptions in brain sensory processing and cognitive performance were seen during sleep fragmentation. Moreover, there is evidence that SF negatively affects memory and learning. Here, significant decreases in GABA and Lactate concentrations were detected in the hippocampus of mice following sleep fragmentation indicating decreased synaptic function in the hippocampus.

Regional differences of metabolites in the rat brain were investigated by using localized in vivo 1H MR spectroscopy at 16.4T. Three regions, thalamus, striatum and hippocampus, were investigated with an ultra-short TE STEAM sequence. The results demonstrated significant variations in all metabolites except aspartate and NAA. The remarkable variation of spectra was the substantially decreased level of the Tau methylene signal at 3.25 ppm in thalamus. The significant increase of the GABA methylene signal at 1.89 ppm was also observed in thalamus.

The effect of different anesthetic agents was investigated in the rat brain by using in vivo 1H NMR spectroscopy. A volume-of-interest was placed in thalamus under two different anesthesia, isoflurane and ketamine/xylazine. The significant increase of glucose was observed in a deep ketamine/xylazine anesthesia while additional metabolic variations on ascorbate, aspartate, glutathione and lactate were detected.

This study was to evaluate alterations in striatum metabolites of rats between anesthetized with isoflurane and ketamine/xylazine in vivo 1H-MRS at 16.4T, and to investigate the appropriateness of anesthetic agents. The concentrations of Ala, Asc, Asp, GABA, Gly and PCr were significantly different between isoflurane and ketamine/xylazine induced groups at the striatum. We demonstrated that metabolites in specific brain region can be differentially influenced according to anesthetic agents. This study showed that the choice of anesthetic is significant in the setting of 1H-MRS. Appropriate anesthetic choice should be pursued to exclude the effect of anesthetic agents on the target area.