Extracellular-intracellular distribution of glucose and lactate in the rat brain assessed noninvasively by diffusion-weighted 1H nuclear magnetic resonance spectroscopy in vivo

To determine the distribution of cerebral glucose and lactate between the intracellular and the extracellular space of the rat brain in vivo, the diffusion characteristic of glucose and lactate was compared with that of metabolites known to be mainly intracellular (N-acetylaspartate, choline, creatine, glutamate, myo-inositol, and taurine) using a pulsed-field-gradient 1H nuclear magnetic resonance technique. The detection of a glucose signal at large diffusion weighting provided direct experimental evidence of intracellular glucose in the rat brain. At large diffusion weighting, the apparent diffusion coefficient (ADC) of glucose and lactate was similar to that of the intracellular metabolites such as N-acetylaspartate, creatine, and glutamate. At small diffusion weighting, the ADC of glucose and lactate was increased, which was explained by a decreased relative contribution of intracellular glucose to the total signal. The calculated extracellular volume fraction of glucose (0.19 ± 0.05) and lactate (0.17 ± 0.06) was consistent with a substantial fraction of glucose and lactate signals being intracellular. The findings were direct in vivo evidence that the largest concentration gradient of glucose is at the blood-brain barrier and that glucose is evenly distributed in the brain in vivo between the intracellular and extracellular space

Metabolic changes in quinolinic acid-lesioned rat striatum detected noninvasively by in vivo 1H NMR spectroscopy

Intrastriatal injection of quinolinic acid (QA) provides an animal model of Huntington disease. In vivo 1H NMR spectroscopy was used to measure the neurochemical profile non-invasively in seven animals 5 days after unilateral injection of 150 nmol of QA. Concentration changes of 16 metabolites were measured from 22 μl volume at 9.4 T. The increase of glutamine ((+25 ± 14)%, mean ± SD, n = 7) and decrease of glutamate (-12 ± 5)%, N-acetylaspartate (-17 ± 6)%, taurine (-14 ± 6)% and total creatine (-9 ± 3%) were discernible in each individual animal (P < 0.005, paired t-test). Metabolite concentrations in control striata were in excellent agreement with biochemical literature. The change in glutamate plus glutamine was not significant, implying a shift in the glutamate-glutamine interconversion, consistent with a metabolic defect at the level of neuronal-glial metabolic trafficking. The most significant indicator of the lesion, however, were the changes in glutathione ((-19 ± 9)%, P < 0.002)), consistent with oxidative stress. From a comparison with biochemical literature we conclude that high-resolution in vivo 1H NMR spectroscopy accurately reflects the neurochemical changes induced by a relatively modest dose of QA, which permits one to longitudinally follow mitochondrial function, oxidative stress and glial-neuronal metabolic trafficking as well as the effects of treatment in this model of Huntington disease. © 2001 Wiley-Liss, Inc

A sustainable reaction process for phase pure LiFeSi2O6 with goethite as an iron source

Lithium-iron methasilicate (LiFeSi$_{2}$O$_{6}$, LFS), a member of clinopyroxene family, is an attractive compound for its multiferroic properties and applicability in energy-related devices. Conventional preparative method requires heating at elevated temperatures for long periods of time, with inevitable severe grain growth. We demonstrate that α-FeO(OH) (goethite) is superior as an iron source toward phase pure LFS over conventional hematite, α-Fe$_{2}$O$_{3}$. The exact phase purity, i.e., no trace of iron containing reactant, is confirmed in the goethite-derived LFS by 57Fe Mössbauer spectroscopy. The grain growth of LFS during heating is suppressed to keep its crystallite size of 120 nm. Higher reactivity of goethite in comparison with hematite is mainly attributed to the dehydration of goethite, which in our case was accelerated by Li$_{2}$O. Related reaction mechanisms with the possible product pre-nucleation during mechanical activation are also mentioned. The magnetic properties of goethite-derived LFS are equivalent to those prepared via a laborious solid-state route. Thus, the presented preparative method offers a more sustainable route than conventional processing, and thus enables practical application of LFS

Proton MRS of the unilateral substantia nigra in the human brain at 4 tesla: Detection of high GABA concentrations

Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra (SN), the cause of which is unknown. Characterization of early SN pathology could prove beneficial in the treatment and diagnosis of PD. The present study shows that with the use of short-echo (5 ms) Stimulated-Echo Acquisition Mode (STEAM) spectroscopy and LCModel, a neurochemical profile consisting of 10 metabolites, including γ-aminobutyric acid (GABA), glutamate (Glu), and glutathione (GSH), can be measured from the unilateral SN at 4 tesla. The neurochemical profile of the SN is unique and characterized by a fourfold higher GABA/Glu ratio compared to the cortex, in excellent agreement with established neurochemistry. The presence of elevated GABA levels in SN was validated with the use of editing, suggesting that partial volume effects were greatly reduced. These findings establish the feasibility of obtaining a neurochemical profile of the unilateral human SN by single-voxel spectroscopy in small volumes. © 2006 Wiley-Liss, Inc

Elevated Pontine and Putamenal GABA Levels in Mild-Moderate Parkinson Disease Detected by 7 Tesla Proton MRS

Background: Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown. Methodology/Principal Finding: To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn &amp; Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. c-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p,0.001 for pons and p,0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls. Conclusion/Significance: The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of th