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Biomedical subjects

J Krane

Publications and source records attributed to J Krane.

At least 19 recordsLinked to original sources
PubMed2006

The iodinated radiographic contrast medium iohexol mimics the vasodilator effect seen with small increases in extracellular K+ in the isolated rabbit central ear artery.

PURPOSE: To investigate whether iodinated radiographic contrast media (IRCM) mimic the hyperpolarizing and vasodilator effects of K+ by comparing the vasodilator effect of a transient rise in extracellular K+ with that of the IRCM iohexol. MATERIAL AND METHODS: Immersed rabbit central ear arterial rings with and without endothelium and pre-contracted with phenylephrine (PE) were used to investigate the dependency of the endothelium in K+-induced vasodilatation. Perfused rabbit central ear arteries, pre-contracted with PE, were used to study the effects of bolus administrations of the IRCM iohexol or KCl on arterial tone under conditions that mimic those employed during clinical arteriography. RESULTS: A small rise in K+ caused an endothelium-independent and ouabain-sensitive relaxation of PE-constricted rabbit central ear artery rings. The relaxation was not changed in the presence of barium. The IRCM iohexol and KCl, injected as boluses into perfused PE-constricted rabbit ear arteries, caused transient decreases in perfusion pressure. Iohexol- and K+-induced pressure decreases were significantly reduced in the presence of 10 microM ouabain alone or in combination with 30 microM barium. Neither iohexol- nor K+-induced pressure decrease was significantly changed in the presence of barium alone compared to controls. CONCLUSION: The vasodilator effect of IRCM mimics the vasodilator effect seen upon small increase in extracellular K+. Under the experimental conditions employed in the present study, a considerable part of the IRCM-induced vasodilatation appears to be due to activation of Na+/K+-ATPase in the smooth muscle cells.

Analysis of Variance↗
PubMed2000

Quantification of plasma lipids and apolipoproteins by use of proton NMR spectroscopy, multivariate and neural network analysis.

New approaches for quantification of human blood plasma lipids and apolipoproteins are presented. One method is based on multivariate analysis of proton nuclear magnetic resonance spectra of human blood plasma. Although similar approaches have been developed previously, this is the first time principal component analysis (PCA) and partial least squares regression (PLS) have been applied to this particular task. Further, a large proportion of the subjects in this study were cancer patients undergoing treatment, which introduced a new dimension to the quantification of lipoprotein distributions. Calibration models for prediction of lipids and apolipoproteins were constructed by use of PLS, and blind samples were used to test the predictive ability. Comparison of the predicted vs observed data obtained by standard clinical chemical procedures gave good agreement; the correlation coefficient for total plasma triglyceride was 0.99, for total plasma cholesterol 0.98, for LDL cholesterol 0. 97, and for HDL cholesterol 0.88. These results are comparable with those obtained with other methods. The quantitative analysis of 14 components (including total cholesterol and total triglyceride) of human blood plasma was also undertaken using various neural network (NN) analyses of selected portions of the spectra. Conventional fully connected backpropagation neural network topologies were capable of providing excellent predictions for the majority of the variables, confirming and reinforcing literature related to this approach. However HDL triglycerides were poorly predicted, while intermediate-quality results were obtained for the LDL cholesterol, plasma apoA1 and LDL apoB variables. In these instances, applying significantly different neural network algorithms involving either general regression or polynomial neural networks in combination with genetic adaptive components for parameter optimisation made improved predictions.

Adult↗
PubMed2000

Improved convection compensating pulsed field gradient spin-echo and stimulated-echo methods.

The need for convection compensating methods in NMR has been manifested through an increasing number of publications related to the subject over the past few years (J. Magn. Reson. 125, 372 (1997); 132, 13 (1998); 131, 126 (1998); 118, 50 (1996); 133, 379 (1998)). When performing measurements at elevated temperature, small convection currents may give rise to erroneous values of the diffusion coefficient. In work with high resolution NMR spectroscopy, the application of magnetic field gradients also introduces an eddy-current magnetic field which may result in errors in phase and baseline in the FFT-spectra. The eddy current field has been greatly suppressed by the application of bipolar magnetic field gradients. However, when introducing bipolar magnetic field gradients, the pulse sequence is lengthened significantly. This has recently been pointed out as a major drawback because of the loss of coherence and of NMR-signal due to transverse relaxation processes. Here we present modified convection compensating pulsed field gradient double spin echo and double stimulated echo sequences which suppress the eddy-current magnetic field without increasing the duration of the pulse sequences.

Magnetic Resonance Spectroscopy↗
PubMed2000

Hyperosmotic perfusion of the beating rat heart and the role of the Na+/K+/2Cl- co-transporter and the Na+/H+ exchanger.

The aim of the present study was to investigate the role of the Na+/K+/2Cl- co-transporter and the Na+/H+ exchanger on contractile function and electrolyte regulation during hyperosmotic perfusion of the heart. Langendorff perfused rat hearts were subjected to hyperosmolal perfusion in 10-min intervals. Perfusates were made hyperosmotic by adding mannitol to the buffer (370, 450 and 600 mOsmol/kg H2O). Cardiac contractile function was monitored with a balloon in the left ventricle (LV) coupled to a pressure transducer. Cardiac effluent was sampled repeatedly throughout and after hyperosmotic perfusion and analysed for content of Na+, K+, and Cl-. All three hyperosmotic perfusates initially reduced LV developed pressure (LVDP), but for 370 and 450 mOsmol/kg H2O, LVDP recovered to baseline within 4 min of perfusion. With 600 mOsmol/kg H2O, LVDP recovered slowly and was 50% below baseline after 10 min of hyperosmotic perfusion. Inhibition of the Na+/H+ exchanger with 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methylsulfonyl-4-piperidinobenzoyl-guanidine methanesulfonate (HOE 694) abolished the recovery of LVDP to the 600 mOsmol/kg H2O perfusate, whereas inhibition of the Na+/K+/2Cl- co-transporter had no impact on LVDP. Potassium was taken up by the heart during hyperosmotic perfusion and this uptake was significantly reduced with inhibition of the Na+/H+ exchanger. Intracellular pH was assessed with 31p magnetic resonance spectroscopy and hyperosmolality induced a significant alkalosis that was dependent upon the Na+/H+ exchanger. The rat heart responds to moderate elevations in osmolality with a transient reduction in contractile function, whereas an elevation of 300 mOsmol/kg H2O persistently reduces contractile function. The Na+/H+ exchanger, but not the Na+/K+/2Cl- co-transporter, is of importance in contractile recovery and electrolyte regulation during hyperosmotic perfusion in the rat heart.

Animals↗
PubMed1999

Detection of dexamethasone in the cornea and lens by NMR spectroscopy.

BACKGROUND: To study the penetration and metabolism of dexamethasone phosphate in the cornea and lens from rabbit following topical administration. METHODS: After topical administration of 0.1, 1 and 10% dexamethasone phosphate solutions, respectively, the cornea and lens were removed and extracted with either perchloric acid (PCA) or with chloroform/methanol to study the lipophilic and hydrophilic metabolites of the drug. The extracts were analyzed with 1H and 19F NMR spectroscopy. RESULTS: Using 19F NMR spectroscopy, both dexamethasone and dexamethasone phosphate were detected simultaneously in the extract of the cornea and lens obtained from the eyes denuded of the epithelium before the treatment. Using 10 and 1% drug solutions, the signals from dexamethasone were also detectable in the 1H NMR spectra among many endogenous metabolites. CONCLUSION: 1H and 19F NMR spectroscopy was shown to be a useful method in the study of penetration and metabolism of dexamethasone in the eye, particularly because both the lipophilic and hydrophilic metabolites of the drug could be detected simultaneously.

Animals↗
PubMed1999

Nuclear magnetic resonance imaging in studies of gravitropism in soil mixtures.

Gravitropic responses of oat coleoptiles were measured in different growth media; humid air, natural soil and artificial soil (glass beads). The oat coleoptiles in soil and glass beads were monitored by NMR imaging, while those in humid air were imaged in darkness with an infrared-sensitive charge-coupled device (CCD) camera. The present study shows for the first time that gravitropic experiments can be performed in artificial soil using NMR imaging as a convenient and suitable recording method. Not only was it possible to follow the gravitropic curvatures in natural soil, but the artificial soil allowed plant images of sufficient spatial and temporal resolution to be recorded. The advantages of using artificial soil in magnetic resonance imaging studies are that the iron content of glass beads is very low compared with natural soil, and that the artificial soil matrix can easily, be standardized with regard to particle size distribution and nutrient content. Two types of glass beads were used, the diameter of the small and the large beads being 300-400 and 420-840 micrometers, respectively. The growth rate of the coleoptiles in soil and in big beads was roughly the same and only slightly lower than in humid air, whereas small beads reduced the growth rate by approx. 16%. The bending rate of the coleoptiles during the gravitropic response was reduced by c. 65% in soil and 75% in bead mixtures relative to bending in air. It should be noted, however, that the maximum curvature of the coleoptile tip was of the same order in all cases, about 35 degrees. This value may represent the largest possible curvature of the organ. The potential of NMR imaging to study, how plant organs penetrate the soil under the influence of gravitropism, mechanical impedance and thigmotropism is also discussed.

Avena↗
PubMed1999

Principal component analysis of proton nuclear magnetic resonance spectra of lipoprotein fractions from patients with coronary heart disease and healthy subjects.

Blood plasma was drawn from 12 healthy subjects and 12 patients with coronary heart disease (CHD). The lipoproteins were fractionated by serial ultracentrifugation. The methyl and methylene regions of proton nuclear magnetic resonance (1 H NMR) spectra of the lipoproteins very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) were analysed by principal component analysis (PCA). Grouping patterns in the score plots and the profiles of the principal components revealed several characteristics of the spectra. LDL subparticle size among the CHD group was consistently skewed against smaller, denser subparticles. This feature was independent of the concentration of LDL cholesterol. Analysis of the LDL spectra by soft independent modelling of class analogy (SIMCA) showed that none of the samples from the CHD group could be assigned as healthy subjects (p < 0.05). We also found that the samples from the healthy subjects were associated with a higher concentration of HDL cholesterol and larger VLDL subparticles. The approach presented, in which PCA is used in combination with NMR spectroscopy, might be implemented in clinical studies to give information about lipoprotein subparticle distribution and lipid content.

Adult↗
PubMed1998

Dexamethasone and dexamethasone phosphate detected by 1H and 19F NMR spectroscopy in the aqueous humour.

To apply nuclear magnetic resonance (NMR) spectroscopy to study the penetration of dexamethasone phosphate into the aqueous humour from rabbit following topical administration. After topical administration of 0.1%, 1.0% and 10% dexamethasone phosphate solutions, respectively, samples of aqueous humour were aspirated, freeze-dried, redissolved in deuterium oxide and analyzed by high resolution 1H and 19F NMR spectroscopy. In order to study the lipophilic and hydrophilic metabolites of the drug, samples obtained after application of 1% dexamethasone phosphate were extracted with methanol/chloroform, and then extracted with perchloric acid. In all samples obtained from eyes denuded of the corneal epithelium prior to administration of dexamethasone, signals corresponding to the chemical shifts of the drug were identified in 19F NMR spectra. In the experiments performed with 1% dexamethasone phosphate, both dexamethasone and dexamethasone phosphate were detected in the aqueous humour. Using 10% dexamethasone phosphate solutions, signals from the drug were detected in 1H NMR spectra simultaneously with signals from about twenty other substances present in the aqueous humour. NMR spectroscopy appears to be a valuable method for studying dexamethasone metabolism and penetration into ocular tissues. It provides simultaneous detection of both the drug metabolites and other substances in the sample and might offer a complementary approach to other analytical methods.

Administration, Topical↗
PubMed1998

Engineering analysis of penile hemodynamic and structural-dynamic relationships: Part I--Clinical implications of penile tissue mechanical properties.

PURPOSE: The least investigated physical determinant of penile rigidity has been penile tissue material properties. The goals in this study (Part I) were to define two penile mechanical parameters, cavernosal expandability X and tunical distensibility VE/VF, determine their magnitudes in humans and develop an analytical expression for penile volume as a function of these two tissue characteristics and intracavernosal pressure. METHODS: Dynamic infusion pharmacocavernosometry was performed in 21 impotent patients (age 43 +/- 19 y) to provide human geometric, hemodynamic and structural data. A mathematically derived model of hemodynamic and structural-dynamic characteristics of penile erection was developed (Parts I, II, III) incorporating penile tissue mechanical qualities. RESULTS: Cavernosal expandability X provided a measure of the ability to approach maximum volume at relatively low intracavernosal pressures. Tunical distensibility VE/VF denoted the maximal erect to flaccid penile volume ratio. The magnitudes of X and VE/VF in the study population were 0.04-0.17 mmHg-1 and 1.7-5.0 respectively. CONCLUSIONS: Enabling penile volume to be derived as a function of tissue mechanical characteristics and pressure, allows for penile rigidity to be expressed (in Part II) as a function of pressure, geometry and tissue qualities.

Adult↗
PubMed1995

Characterization of plasma lipids in patients with malignant disease by 13C nuclear magnetic resonance spectroscopy and gas liquid chromatography.

The purpose of this study was to characterize possible changes in fatty acid composition of plasma lipids associated with malignancy. The very low, low, and high-density lipoproteins were isolated by gradient density ultracentrifugation of plasma from 16 patients with malignant disease and from 15 controls. The triglyceride, esterified cholesterol, and phospholipid constituents of each lipoprotein fraction were isolated, and the fatty acid composition within each lipid component was determined by gas liquid chromatography (GLC). In the 10- to 45-parts-per-million (ppm) region of the carbon-13 (13C) nuclear magnetic resonance (NMR) plasma spectrum, differences were found between patients with malignant disease and controls. The ratio of the 31.6/32.1 ppm resonance intensities was lower in the group of cancer patients. The ratio of the 24.4/24.9 ppm resonance intensities in patients with malignant disease was different from the nonpregnant controls. The NMR changes were interpreted in light of GLC data that indicated derangements in the composition of fatty acids within lipoprotein lipids. In total plasma esterified cholesterol, the relative amount of linoleic acid (18:2, n-6) was lower, whereas oleic acid (18:1, n-9) was higher in the group of patients with malignant disease. In total plasma triglycerides, the amount of oleic acid was higher in the cancer patient group. For total plasma phospholipids, no differences in fatty acid composition between patients and controls were found. Throughout the lipoprotein fractions, the same differences in oleic acid and linoleic acid distribution for triglyceride and esterified cholesterol were found when comparing cancer and control subjects. In conclusion, we found that there are certain differences in the 13C NMR spectra and fatty acid profiles between a small and heterogeneous group of cancer patients after they have received their initial treatment and a group of healthy controls. We suggest that carbon NMR spectroscopy could be useful in characterizing malignancy-associated lipid changes.

Adult↗
PubMed1995

Plasma changes in breast cancer patients during endocrine therapy--lipid measurements and nuclear magnetic resonance (NMR) spectroscopy.

Side-effects following long-term endocrine therapy might have clinical implications. The aim of this study was to study potential methods to detect effects on plasma induced by hormonal therapies. The composite methylene (chemical shift between 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) aliphatic peaks of the 1H magnetic resonance spectrum (500 MHz) were analysed in consecutive plasma samples of 23 cancer patients drawn before and during treatment with hormonally acting drugs. The aliphatic peaks were analyzed for line width at half-height and then averaged. In addition, 13C magnetic resonance spectroscopy (125 MHz) analyses were done in selected patients. The blood samples were analyzed for triglyceride, cholesterol, apolipoprotein A1 (apo A1), and apolipoprotein B (apo B) levels. The methylene line width increased significantly after 9 weeks of tamoxifen (41.4 vs. 37.6 Hz). A trend of differences was observed in the saturated part of the 13C magnetic resonance spectrum. A significant decrease in total cholesterol (mean decrease, 13%), increases in apo A1 (9%) and in the ratio of apo A1 to apo B (28%), but unchanged total triglycerides were found, indicating a decrease in LDL and increase in HDL lipoproteins in these patients following tamoxifen therapy. During dose escalation with the aromatase inhibitor exemestane, the methylene line width seemed to decrease (31.9 vs 38.8 Hz, at 12 weeks and baseline, respectively). Significant decreases in total (13%) and HDL (32%) cholesterol, apo A1 (25%), and total triglyceride (16%) levels were found during the same interval. The apo A1/apo B ratio decreased by 25%. For patients on dexamethasone, the proton aliphatic line widths increased one day after the initiation of therapy. The changes in line shape observed during dexamethasone therapy indicated lower levels of triglyceride-rich relative to triglyceride-poor lipoproteins, consistent with results from the lipid analyses. In conclusion, nuclear magnetic resonance spectroscopy might have potential to detect effects on plasma induced by endocrine therapy. The lipid analyses in these patients were in support of the changes in lipid profile as evaluated by nuclear magnetic resonance spectroscopy.

Androstadienes↗
PubMed1994

1H NMR spectroscopic characterization of perchloric acid extracts from breast carcinomas and non-involved breast tissue.

High-resolution 1H NMR spectra were obtained from perchloric acid extracts of breast tumor specimens and adjacent non-involved tissue. Two-dimensional shift-correlated and homonuclear J-resolved spectroscopy were used to identify coupled resonances in the spectra. Chemical shifts, multiplicities and spin-spin coupling constants of several non-resolved resonances in the one-dimensional spectra could be determined by the two-dimensional methods. Several differences in the metabolite content of the two types of extracts were established. The spectra of extracts from non-involved tissue were dominated by signals from glucose and other carbohydrates, while most of the tumors had very low or no detectable levels of glucose. High concentrations of lactate, taurine and succinate, an increase of the phosphocholine level, and a very low phosphocreatine level were characteristic findings in the 1H spectra of tumor extracts. The variation in the level of myo-inositol follows the variation in glucose for the two types of tissue. Scyllo-inositol was for the first time observed in the NMR spectra from breast tissue. Uridine 5'-diphospho-N-acetylglucosamine and uridine 5'-diphospho-N-acetylgalactosamine have been identified and there is an increased level of these two hexoses in the tumor tissue. These results provide insight into breast tumor metabolism, by simultaneously detecting a large number of metabolites and demonstrate the potential for using 1H NMR spectroscopy for studying different metabolic pathways in breast tumors. At the same time they provide useful information for interpretation of in vivo 1H NMR spectra of breast tumors.

Breast↗
PubMed1993

NMR and molecular dynamics study of the tripeptide L-pyroglutamyl-L-histidylglycine.

The 1H spectrum of L-pyroglutamyl-L-histidylglycine in DMSO-d6 and 1H and 13C NMR spectra in D2O at pH 4.26 to 8.90 have been analysed. 3JHH vicinal coupling constants were used to determine rotamer populations by means of the Karplus equation. Viable molecular geometries were obtained with the aid of molecular dynamics simulations including water as solvent. In DMSO and in aqueous solution at low pH two stable conformations were identified which both have an intramolecular hydrogen bond between the histidine side chain and the C-terminal carboxylate group.

Amino Acid Sequence↗
PubMed1993

Early changes in the 1H-NMR plasma spectrum in patients following breast surgery.

The composite methylene (chemical shift between 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) resonances of the 1H-nuclear magnetic resonance (NMR) spectrum were analysed in plasma samples drawn pre- and post-surgery from patients treated for benign or malignant breast tumor. Using a 500 MHz NMR instrument operating at 25 degrees C, the resonances were analysed for line width at half-height and then averaged. The amounts of triglyceride (TG), cholesterol, apolipoproteins A1 (ApoA1) and B (ApoB) were measured in each sample. One week post-surgery, the high-field shoulder of the aliphatic peaks decreased and the composite peaks were weighted down-field compared with spectra obtained pre-surgery. The average line width in patients with malignant tumor observed 1 week post-surgery was narrower than pre-surgery (30.5 +/- 3.9 vs 38.1 +/- 4.2 Hz) (P = 0.01). Line widths observed 1 day post-surgery were not significantly different from pre-surgery values in either patient group. Comparing the methylene and methyl composite peaks, the narrowing in line width observed 1 week post-surgery was more pronounced for the methylene than the methyl line width. The ratio between the height of the composite methylene and methyl peaks was higher 1 week post-surgery (ratio, 2.12 +/- 0.23) than pre-surgery (1.79 +/- 0.37) (P = 0.03), indicative of a relative increase in triglyceride-rich lipoproteins. Compared with pre-surgery levels, TG was higher (1.8 +/- 0.3 vs 1.5 +/- 0.4 mmol/l) (P = 0.05) and ApoA1 lower (1.32 +/- 0.14 vs 1.43 +/- 0.12 g/l) (P = 0.02) 1 week post-surgery. One day post-surgery, decreased levels of lipids and apoliproteins were found. In conclusion, the line narrowing is explained as an effect of the surgical trauma itself. A less contribution to the composite line from high-density (HDL) relative to very-low-density (VLDL) lipoprotein is suggested as one mechanism for line width narrowing observed after surgery.

Adult↗
PubMed1992

1H NMR study of cortex neurons and cerebellar granule cells on microcarriers and their PCA extracts: lactate production under hypoxia.

Lactate production of 6-day-old cerebral cortex neurons and 7-day-old cerebellar granule cells from mouse brain attached to cytodex 3 microcarriers was studied as a function of time, under hypoxic conditions using 1H NMR. Perchloric acid extracts of both cell types were prepared and 1H NMR spectra showed compounds characteristic for these neurons. In particular the granule cell extracts showed a large amount of glutamate as expected from biochemical experiments, whereas the cortex neurons showed a large amount of 4-aminobutyric acid.

Animals↗
PubMed1992

Proton magnetic resonance spectroscopy of fractionated plasma lipoproteins and reconstituted plasma from healthy subjects and patients with cancer.

Proton nuclear magnetic resonance spectra at 500 MHz of plasma and the very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions isolated by KBr gradient ultracentrifugation were analysed in 16 cancer patients, six pregnant and nine non-pregnant healthy subjects. In spectra with narrow plasma composite aliphatic peaks (methylene at 1.2-1.4 p.p.m. and methyl at 0.8-0.9 p.p.m., respectively), a relative increase in either VLDL, LDL, or both, or a decrease in HDL signals was observed. The mechanism for line-width narrowing seemed different in cancer patients (less signals from HDL relative to VLDL) compared with pregnant women (more signals from LDL). By reconstitution of plasma samples from both healthy subjects and patients with malignant disease, decreased concentration of VLDL or HDL resulted in broadening or narrowing of the composite peaks, respectively. The effects of VLDL and HDL on the plasma line width were moderated by the signals from LDL. Within lipoprotein fractions, the methylene and methyl resonances were shifted to a higher field with increased observation temperature, the change in shift being greatest for HDL. The line width of composite peaks in plasma varied with the observation temperature, depending on the relative concentrations of individual lipoproteins. The correlation coefficient (r) for the relation between total plasma triglyceride level and the average of the line-width of the composite methylene and methyl peaks was -0.78 (p less than 0.001). For spectra of individual lipoproteins, statistical significant relationships were found between line-widths and triglyceride content of the LDL fraction (methyl line-width, r = -0.63) (p less than 0.001) and between methylene line-width and cholesterol of HDL (r = 0.54) (p = 0.003). In summary, the shape and width of the composite aliphatic peaks of plasma were affected by the relative concentration, chemical shift and transition temperature of both VLDL, LDL, and HDL, and by the total triglyceride level. Comparing pregnancy and malignant disease, the lipoprotein resonances contributed differently in giving narrow composite signals.

Female↗
PubMed1991

First direct demonstration of preferential release of citrate from astrocytes using [13C]NMR spectroscopy of cultured neurons and astrocytes.

Primary cultures of cerebral cortical neurons or astrocytes or the two cell types together (co-cultures) were incubated with [1-13C]glucose for 20 or 48 h. Subsequently, perchloric acid (PCA) extracts of the cells as well as redissolved lyophilized media were subjected to NMR spectroscopy in order to detect 13C-labeled amino acids (glutamine, glutamate, gamma-aminobutyrate (GABA)) and other metabolites (lactate, tricarboxylic acid cycle (TCA) constituents). NMR spectra of PCA extracts of neurons or co-cultures exhibited distinct peaks for glutamate and GABA whereas the PCA extracts of astrocytes and co-cultures showed peaks corresponding to glutamine and glutamate. This pattern is consistent with the neuronal location of the GABA synthesizing enzyme glutamate decarboxylase and the astrocytic localization of the glutamine synthesizing enzyme, glutamine synthetase. NMR spectra of the incubation media showed clearly that 13C-labeled citrate, alanine and glutamine were synthesized and released from astrocytes since only media from the astrocyte cultures or co-cultures or neurons and astrocytes contained these metabolites in detectable amounts. It may be concluded that astrocytes play an important role supplying neurons with precursors for biosynthesis of glutamate and GABA such as glutamine and TCA cycle constituents. Since among the latter only citrate could be found in significant amounts it may be hypothesized that this may be the quantitatively most important TCA constituent to be released from astrocytes and subsequently utilized by neurons.

Animals↗