Amino Acid Concentrations in Cerebrospinal Fluid

Heiblim, David I.; Evans, Hugh E.; Glass, Leonard; Agbayani, Melanie M.

doi:10.1001/archneur.1978.00500350069015

Cited by 42 publications

(13 citation statements)

References 11 publications

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“…The CSF concentrations of two amino acids that do not have a documented neurotransmitter function (serine and threonine) did not change during infection. These findings extend previous studies that have documented increased CSF concentrations of glutamate, aspartate, glycine, taurine, and alanine in patients with bacterial meningitis (18,20). Increased concentrations of other individual amino acids, as well as of the total concentration of amino acids, have also been observed in patients with meningitis (17,19,28).…”

Section: Discussionsupporting

confidence: 91%

“…A first report in 1975 found increased levels of glutamic acid, glutamine, and y-aminobutyric acid in the CSF of patients with bacterial meningitis (1 7). Other authors have also reported abnormal CSF concentrations of amino acids, but the importance of these changes has not been explored in detail (18)(19)(20). Importantly, it is not known whether amino acid concentrations in the CSF reflect changes occurring in the brain interstitial fluid, the medium relevant for the potential neurotoxicity of EAA.…”

Section: The Infectious Diseases Laboratories [Lg-r Jh T Mamentioning

confidence: 99%

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Amino Acids in Cerebrospinal and Brain Interstitial Fluid in Experimental Pneumococcal Meningitis

et al. 1993

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ABSTRACT. Excitatory amino acids are increasingly implicated in the pathogenesis of neuronal injury induced by a variety of CNS insults, such as ischemia, trauma, hypoglycemia, and epilepsy. Little is known about the role of amino acids in causing CNS injury in bacterial meningitis. Several amino acids were measured in cerebrospinal fluid and in microdialysis samples from the interstitial fluid of the frontal cortex in a rabbit model of pneumoccocal meningitis. Cerbrospinal fluid concentrations of glutamate, aspartate, glycine, taurine, and alanine increased significantly in infected animals. Among the amino acids with known excitatory or inhibitory function, interstitial fluid concentrations of glutamate were significantly elevated (by 470%).Alanine, a marker for anaerobic glycolysis, also increased in the cortex of infected rabbits. The elevated glutamate concentrations in the brain extracellular space suggest that excitotoxic neuronal injury may play a role in bacterial meningitis. (Pediatr Res 33: 510-513, 1993) Abbreviations CSF, cerebrospinal fluid EAA, excitatory amino acid cfu, colony-forming unit poorly understood. Cerebral blood flow studies in humans and experimental animals with bacterial meningitis suggest that, after an initial hyperemic phase (13), ischemia occurs under certain circumstances and may contribute to the development of neuronal injury (14-16). As with other forms of ischemia-induced CNS injury it is conceivable that the harmful effects of ischemia could be potentiated by EAA during meningitis.A few studies have examined concentrations of amino acids in CSF in bacterial meningitis. A first report in 1975 found increased levels of glutamic acid, glutamine, and y-aminobutyric acid in the CSF of patients with bacterial meningitis (1 7). Other authors have also reported abnormal CSF concentrations of amino acids, but the importance of these changes has not been explored in detail (18)(19)(20). Importantly, it is not known whether amino acid concentrations in the CSF reflect changes occurring in the brain interstitial fluid, the medium relevant for the potential neurotoxicity of EAA. To test the hypothesis that changes in amino acids may play a role in CNS injury during meningitis, we measured in the present study brain interstitial fluid concentrations of several amino acids in a rabbit model of pneumoccoca1 meningitis and determined whether changes similar to those observed in the CSF during meningitis occur in the brain. Interstitial fluid concentrations of amino acids were measured in the cortex because of its proximity to the inflammation in the subarachnoid space and because pathologic changes were primarily found in the cortex in a recent histopathologic study in rats with experimental pneumococcal meningitis (2 1).EAA, physiologic neurotransmitters in the mammalian CNS, are increasingly implicated in the pathogenesis of neuronal injury induced by a variety of CNS insults, such as global and focal ischemia, brain and spinal cord trauma, hypoglycemia, and epilepsy (1-7). There is good...

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Section: Discussionsupporting

confidence: 91%

Section: The Infectious Diseases Laboratories [Lg-r Jh T Mamentioning

confidence: 99%

Amino Acids in Cerebrospinal and Brain Interstitial Fluid in Experimental Pneumococcal Meningitis

et al. 1993

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“…In 3 out of 22 patients, we found very high levels of the excitatory amino acids aspartate and/or glutamate exceeding the normal values for these amino acids in cerebrospinal fluid (Blau et al, 2003;Gjessing et al, 1972;Heiblim et al, 1978 and references cited therein) by at least 10-fold for aspartate and at least 7-fold for glutamate. These include patient 6 (focal cortical dysplasia; aspartic acid 94 mol/l, glutamic acid 215 mol/l); patient 20 (anaplastic oligoastrocytoma WHO grade III; aspartic acid undetectable, glutamic acid 1264 mol/l); and patient 3 (metastasis of mamma carcinoma; aspartic acid 59 mol/l, glutamic acid 766 mol/l).…”

Section: Resultsmentioning

confidence: 61%

“…These include patient 6 (focal cortical dysplasia; aspartic acid 94 mol/l, glutamic acid 215 mol/l); patient 20 (anaplastic oligoastrocytoma WHO grade III; aspartic acid undetectable, glutamic acid 1264 mol/l); and patient 3 (metastasis of mamma carcinoma; aspartic acid 59 mol/l, glutamic acid 766 mol/l). The normal range in cerebrospinal fluid for aspartic acid is 0.4-5.2 mol/l (Blau et al, 2003), for glutamic acid published values range from 1.7 ± 0.9 mol/l to 14.7 ± 13.3 mol/l (see Gjessing et al, 1972;Heiblim et al, 1978). Of the three patients, patients 6 and 20 experienced seizures before the operation, while patient 3 did not report the occurrence of seizures.…”

Section: Resultsmentioning

confidence: 98%

Amino acid composition of brain cysts: levels of excitatory amino acids in cyst fluid fail to predict seizures

Wieser¹,

Rudolph²,

Blau³

et al. 2003

Epilepsy Research

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“…Since lumbar puncture is not justified in normal children, we had to compare the quantitative results obtained for meningitis cases with the CSF samples of children suffering from other disorders that were subsequently grouped as controls (n ¼ 24) as per the earlier reported works. 62,63 Examination of the 1 H NMR spectra proved the distinctive presence of glutamine and the relative absence of glutamate in all 167 meningitis CSF samples, which is a somewhat striking feature. This is in sharp contrast to the findings of an earlier report that described the measurement of glutamine and glutamate in the CSF of meningitis-affected children using electrophoresis.…”

Section: Discussion Nmr Spectroscopic Findings and Clinical Observationsmentioning

confidence: 93%

Proton MR CSF analysis and a new software as predictors for the differentiation of meningitis in children

et al. 2004

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This article describes proton MR spectroscopic analysis of cerebrospinal fluid of 167 children suffering from meningitis and 24 control cases. Quantification of 12 well-separated and commonly observed cerebrospinal fluid metabolites viz., -hydroxybutyrate, lactate, alanine, acetate, acetone, acetoacetate, pyruvate, glutamine, citrate, creatine/creatinine, glucose (total) and urea was carried out using Bruker's NMRQUANT software with respect to a known concentration of sodium-3-(trimethylsilyl)-2,2,3,3-d 4 -propionate (TSP), serving as an external reference. The assignment of urea in CSF is reported for the first time by NMR. The presence of cyclopropane, observed for the first time in tuberculous meningitis overall in 85.1% of cases, acts as a finger-print marker for the differential diagnosis. Multivariate discriminant function analysis was carried out for the proton MR-detected metabolite information and the clinical symptoms data of the meningitis and control cases to find the important descriptors for classification, followed by a re-validation of the entire database. It was found that the control could be differentiated from the disease group with a success rate of 96.4%, followed by the differential diagnosis of tuberculous meningitis with a corresponding value of 77.2%. Excluding the presence of cyclopropane, bacterial meningitis could be classified 84.4% correct and viral meningitis with a rate of 83.3%. It is proposed that the NMR spectroscopic information, along with other routine clinical features, may serve as an additional diagnostic tool for the differential diagnosis of meningitis in children.

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Amino Acid Concentrations in Cerebrospinal Fluid

Cited by 42 publications

References 11 publications

Amino Acids in Cerebrospinal and Brain Interstitial Fluid in Experimental Pneumococcal Meningitis

Amino Acids in Cerebrospinal and Brain Interstitial Fluid in Experimental Pneumococcal Meningitis

Amino acid composition of brain cysts: levels of excitatory amino acids in cyst fluid fail to predict seizures

Proton MR CSF analysis and a new software as predictors for the differentiation of meningitis in children

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