Little change in cerebrospinal fluid amino acids in subtypes of multiple sclerosis compared with acute polyradiculoneuropathy.

Levels of free amino acids were determined in randomised, blinded samples of cerebrospinal fluid (CSF) from patients with relapsing-remitting or chronic progressive multiple sclerosis (MS), all in the active phase of disease. The levels were compared with amino acid amounts in patients with an acute polyradiculoneuropathy (Guillain-Barré syndrome (GBS)) and a control population of patients with no known neurological disease or deficit. The data did not indicate any significant changes in amino acid levels between MS subgroups. The only significant differences between MS patients and controls were a modest reduction in glutamate and a slight increase in taurine, but the changes were so small that the biological relevance is dubious. These results contrasted with the marked increases for many amino acids in CSF from patients with acute polyradiculoneuropathy compared with controls. The amino acid profile in cerebrospinal fluid (CSF) does not appear to provide evidence of differential pathology in multiple sclerosis (MS). The increase in hydrophobic amino acids and lysine in CSF from patients with acute polyradiculoneuropathy is consistent with transudation over the blood-CSF barrier following an infection. The increases in glutamine and alanine may reflect increased nitrogen removal from brain.

Proton magnetic resonance spectroscopy of cerebrospinal fluid in neurodegenerative disease: indication of glial energy impairment in Huntington chorea, but not Parkinson disease.

Metabolite levels in cerebrospinal fluid from patients with Parkinson disease or Huntington chorea were compared with the levels in healthy controls using proton magnetic resonance spectroscopy. No significant differences were found for any metabolite measured in cerebrospinal fluid from patients with Parkinson disease compared to controls. Slight but significantly reduced levels of both lactate and citrate, however, were found in cerebrospinal fluid from patients with Huntington chorea compared to controls. This suggests possible impairment of both glycolysis and tricarboxylic acid cycle function. The reduction in lactate found in the present study may reflect neuronal loss. The decrease in citrate supports the theory of mitochondrial dysfunction in the brain of patients with Huntington chorea, but also suggests that there may be an important astrocytic component in this disease. If so, it would certainly have implications for neuronal function.

Amino acid neurotransmitter metabolism in neurones and glia following kainate injection in rats.

Limbic seizure was induced in rats by intraperitoneal injection of the glutamate receptor agonist kainic acid. After 14 days [1-13C]glucose and [1,2-13C]acetate were injected subcutaneously and the rats killed 15 min later. Analysis of brain extracts was performed using 13C-magnetic resonance spectroscopy and high performance liquid chromatography. No significant differences between the two groups of rats were found for label concentration in blood or total metabolite tissue levels. Only astrocytes are able to utilize acetate as a substrate, whereas glucose is thought to be metabolized predominantly in the neuronal tricarboxylic acid cycle. Thus information about neuronal and astrocytic metabolism could be obtained in the same animal. A significant increase in label derived from [1-13C]glucose was observed in metabolites such as glutamate, gamma-aminobutyric acid, aspartate, and succinate (all of which are mainly labelled in neurones). The increased labelling of glutamine in epileptic rats might be due to transfer of labelled glutamate from neurones to astrocytes. Astrocytic metabolism of acetate and transfer of glutamine to neurones were not affected. The results suggest that increased neuronal activity 2 weeks following epileptic seizures produces increased amino acid turnover in neurones. Changes in astrocytic metabolism were not detected.

Nuclear magnetic resonance spectroscopy of cerebrospinal fluid from patients with low back pain and sciatica.

STUDY DESIGN: This study was carried out to assess the metabolic differences between pain-free control subjects and patients with low back pain, either with or without disc protrusion or herniation. OBJECTIVES: To analyze various metabolites in human cerebrospinal fluid using proton nuclear magnetic resonance spectroscopy. The potential use of this technique as an additional tool for diagnostic assessment was also evaluated. SUMMARY OF BACKGROUND DATA: Inflammation is thought to play a major role in the generation of lumbar spine pain, a theory supported both by animal and in vitro studies. The effect of the inflammation in terms of increased metabolism has not yet been studied. METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture, frozen, redissolved, and analyzed for metabolites by proton nuclear magnetic resonance spectroscopy. RESULTS: Significantly lower values for several key metabolites were found in patients with low back pain or sciatica, with the lowest values in the subgroup of patients with myelographic signs of disc protrusion or herniation. CONCLUSIONS: The results indicate a higher level of metabolic activity in patients with low back pain or sciatica compared with pain-free control subjects, with this difference being most pronounced in the subgroup of patients with myelographic evidence of disc protrusion or herniation.

Cerebrospinal fluid lactate and glutamine are reduced in multiple sclerosis.

OBJECTIVES: To analyse various metabolites in human cerebrospinal fluid from healthy controls and patients with multiple sclerosis. PATIENTS AND METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture, frozen, redissolved, and analysed for metabolites by proton nuclear magnetic resonance spectroscopy. RESULTS: Significantly lower values for lactate and glutamine were found in patients with multiple sclerosis in comparison with controls. No significant differences were found between patients with the relapsing-remitting and chronic progressive forms of the disease for any of the metabolites measured. CONCLUSION: There is a concomitant reduction in both lactate and glutamine in the cerebrospinal fluid of patients with multiple sclerosis compared to controls. This may be related to altered astrocytic metabolism during the disease. The results clearly show the diagnostic potential of magnetic resonance spectroscopy in diseases such as multiple sclerosis.

Comparison of extracellular matrix in human osteosarcomas and melanomas growing as xenografts, multicellular spheroids, and monolayer cultures.

BACKGROUND: The composition of extracellular matrix in human xenografts and spheroids were compared with the monolayer cultures from which they originated. Collagen I, fibronectin, acetylglucosamine, and acetylgalactosamine were quantitated in two osteosarcomas and one melanoma. METHODS: Using fluorescence microscopy, extracellular matrix constituents in the cellular and extracellular compartment were measured, whereas flow cytometry measured the extracellular matrix constituents bound to the cell surface as well as the total cellular amount including intracellular and surface bound constituents. RESULTS: The fluorescence microscopy measurements, demonstrated that the xenografts contained more or equal quantities of the extracellular matrix constituents compared with the spheroids. Flow cytometric measurements of total cellular amounts, showed that cells from xenografts usually contained more or equal amounts as the spheroid cells, which contained less or equal amounts as the monolayer cells. The surface expression of the extracellular matrix constituents increased or there were no significant differences, comparing cells grown as monolayers, spheroids, and xenografts. CONCLUSIONS: The data shows that multicellular spheroids being an in vitro system of intermediate complexity between monolayer cultures and tumours, contain an extracellular matrix corresponding to some degree to this intermediate position.