Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 39
Filter
1.
J Alzheimers Dis ; 78(3): 1229-1236, 2020.
Article in English | MEDLINE | ID: mdl-33104030

ABSTRACT

BACKGROUND: Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma. OBJECTIVE: Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels. METHODS: This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-ß (Aß) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models. RESULTS: No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aß42, T-tau, P-tau, and CSF/serum albumin ratios (p < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOEɛ4 carriers. CONCLUSION: CSF iron levels are elevated with cerebral microbleeds in APOEɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Cerebral Small Vessel Diseases/cerebrospinal fluid , Cognitive Dysfunction/cerebrospinal fluid , Dementia, Vascular/cerebrospinal fluid , Metals, Heavy/cerebrospinal fluid , Aged , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/genetics , Amyloid beta-Peptides/cerebrospinal fluid , Apolipoprotein E2/genetics , Apolipoprotein E4/genetics , Cerebral Hemorrhage/cerebrospinal fluid , Cerebral Hemorrhage/diagnostic imaging , Cerebral Small Vessel Diseases/diagnostic imaging , Chromium/cerebrospinal fluid , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/genetics , Copper/cerebrospinal fluid , Dementia, Vascular/diagnostic imaging , Diagnostic Self Evaluation , Female , Humans , Iron/cerebrospinal fluid , Magnetic Resonance Imaging , Male , Manganese/cerebrospinal fluid , Middle Aged , Nickel/cerebrospinal fluid , Peptide Fragments/cerebrospinal fluid , Phosphorylation , Zinc/cerebrospinal fluid , tau Proteins/cerebrospinal fluid
2.
J Trace Elem Med Biol ; 49: 164-170, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29472131

ABSTRACT

BACKGROUND: Parkinson's disease is affecting about 1% of the population above 65 years. Improvements in medicine support prolonged lifetime which increases the total concentration of humans affected by the disease. It is suggested that occupational and environmental exposure to metals like iron (Fe), manganese (Mn), copper (Cu) and zinc (Zn) can influence the risk for Parkinson's disease. These metals play a key role as cofactors in many enzymes and proteins. METHODS: In this case-control study, we investigated the Mn-, Fe-, Cu- and Zn-species in cerebrospinal fluid (CSF) by size-exclusion chromatography hyphenated to inductively coupled plasma mass spectrometry (SEC-ICP-MS) and the total concentration of these metals by inductively coupled plasma sector field mass spectrometry (ICP-sf-MS). RESULTS: The investigation of total metal concentration and speciation provided only minor changes, but it produced strong significance for a number of ratios. The analysis revealed a strong change in the ratio between total concentration of Fe and the amino acid-fraction of Cu. This could be observed when analyzing both the respective element concentrations of the fraction (which also depends on individual variation of the total element concentration) as well as when being expressed as percentage of total concentration (normalization) which more clearly shows changes of distribution pattern independent of individual variation of total element concentrations. CONCLUSION: Speciation analysis, therefore, is a powerful technique to investigate changes in a case-control study where ratios of different species play an important role.


Subject(s)
Amino Acids/cerebrospinal fluid , Copper/cerebrospinal fluid , Parkinson Disease/cerebrospinal fluid , Aged , Case-Control Studies , Chromatography, Gel , Female , Humans , Iron/cerebrospinal fluid , Male , Manganese/cerebrospinal fluid , Mass Spectrometry , Middle Aged , Zinc/cerebrospinal fluid
3.
Neurosci Lett ; 665: 92-98, 2018 02 05.
Article in English | MEDLINE | ID: mdl-29191695

ABSTRACT

Whether systemic manganese (Mn) dysfunctions in Parkinson's Disease (PD) is still under ongoing debate. The recent reported studies on the circulating Mn levels in PD showed inconsistent results. A meta-analysis study was conducted to evaluate the association of circulating Mn levels with PD, and to clarify whether Mn should be considered as a potential risk factor for PD. A systematic searching was performed based on PubMed, web of science, and China National Knowledge Infrastructure (CNKI). Finally, 22 studies were identified, involving 637 PD patients and 802 health controls (HC) individuals for serum Mn, 1258 PD patients and 1304 HC individuals for peripheral blood Mn, and 195 PD patients and 196 HC individuals for cerebrospinal fluid (CSF) Mn. Forest plots were adopted to represent the comparison of the groups by assessing standardized mean difference with random effects model. This meta-analysis revealed a significantly increased serum Mn levels in PD patients (SMD=0.78; 95% CI [0.32, 1.24]; P=0.001), and it was further confirmed when serum, plasma and whole blood studies were analyzed together (SMD=0.58; 95% CI [0.25, 0.91]; P=0.001). Instead, no significant differences of CSF Mn were observed between PD patients and HC individuals (SMD=-0.09; 95% CI [-0.47, 0.29]; P=0.644). These results supported the notion that elevated Mn level should be a potential risk factor for PD, although the high heterogeneity and methodological limitations recommended caution in the interpretations for the present findings.


Subject(s)
Ions/blood , Manganese/blood , Manganese/cerebrospinal fluid , Parkinson Disease/blood , Parkinson Disease/cerebrospinal fluid , Aged , China , Female , Homeostasis/physiology , Humans , Male , Middle Aged , Risk Factors
4.
J Clin Lab Anal ; 31(6)2017 Nov.
Article in English | MEDLINE | ID: mdl-28205254

ABSTRACT

BACKGROUND: The homeostasis of essential trace elements such as selenium and manganese may be altered in patients with severe diseases of various etiologies (trauma brain injuries, tumors, leukemias, lymphomas, neurological diseases). METHODS: Concentration of manganese and selenium were determined in cerebrospinal fluid by electrothermal atomic absorption spectrometry in 50 hospitalized children with various clinical ethiologies including oncological, neurological, and brain related diseases. RESULTS: The concentrations of manganese in cerebrospinal fluid of children were 0.97±0.67 µg/L. The concentrations of selenium were 13.3±3.5 µg/L. The concentrations were similar as published in adults. The values did not correlated with the age, gender and severity of the disease. CONCLUSION: We evaluated values of selenium and manganese in cerebrospinal fluid of seriously diseased children.


Subject(s)
Manganese/cerebrospinal fluid , Selenium/cerebrospinal fluid , Adolescent , Brain Diseases/cerebrospinal fluid , Child , Child, Preschool , Critical Illness , Female , Humans , Infant , Limit of Detection , Linear Models , Male , Neoplasms/cerebrospinal fluid , Spectrophotometry, Atomic
5.
Anal Bioanal Chem ; 405(7): 2301-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23325402

ABSTRACT

Occupational manganese (Mn) overexposure leads to accumulation in the brain and has been shown to cause progressive, permanent, neuro-degenerative damage with syndromes similar to idiopathic Parkinsonism. Mn is transported by an active mechanism across neural barriers (NB) finally into the brain; but to date, modes of Mn neurotoxic action are poorly understood. This paper investigates the relevant Mn-carrier species which are responsible for widely uncontrolled transport across NB. Mn speciation in paired serum/cerebrospinal fluid (CSF) samples was performed by size exclusion chromatography-inductively coupled plasma-dynamic reaction cell-mass spectrometry (SEC-ICP-DRC-MS) and capillary zone electrophoresis coupled to ICP-DRC-MS in a 2D approach for clear identification. For additional species verification, electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry was used after SEC-ICP-DRC-MS (second 2D approach). The Mn species from the different sample types were interrelated and correlation coefficients were calculated. In serum protein-bound Mn species like Mn-transferrin/albumin (Mn-Tf/HSA) were dominant, which had the main influence on total Mn in serum if Mn(total) was <1.5 µg/L. Above serum Mn(total) concentration of 1.6 µg/L the serum Mn(total) concentration was correlated with increasing Mn-citrate (Mn-Cit) concentration. In parallel Mn(total) and Mn species in CSF were determined. It turned out that Mn(total) from CSF was about half of Mn(total) in serum; Mn-Tf/HSA was only about 10% compared to serum. It turned out that above 1.6 µg/L Mn(total) in serum Mn-Cit was not only the leading Mn species in serum but also was the main influencing factor of both Mn(total) and Mn-Cit concentration in CSF. These results were further investigated using two statistical models (orthogonal partial least squares discriminant analysis, canonical discriminant analysis). Both models discriminated the samples in two groups where CSF samples were either correlated to Mn(total) and Mn-Cit (samples with serum Mn(total) > 1,550 ng/L) or correlated to Mn-Tf/HSA (samples with serum Mn(total) < 1,550 ng/L). We conclude that elevated Mn-Cit(serum) could be a valuable marker for increased total Mn in CSF (and brain), i.e., it could be a marker for elevated risk of Mn-dependent neurological disorders such as manganism in occupational health.


Subject(s)
Chromatography, Gel/methods , Electrophoresis, Capillary/methods , Manganese/blood , Manganese/cerebrospinal fluid , Mass Spectrometry/methods , Biological Transport , Female , Humans , Nervous System Diseases/blood , Nervous System Diseases/cerebrospinal fluid
6.
Exp Biol Med (Maywood) ; 237(7): 803-10, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22859739

ABSTRACT

Neurotoxic properties of manganese (Mn) are well documented. It is less known that Mn contributes to the development of neurodegenerative disorders in the general population. This study presents Mn data from patients with amyotrophic lateral sclerosis (ALS) in a well-defined cohort diagnosed by electrophysiological methods. Cerebrospinal fluid (CSF) and plasma were collected from patients and controls. Mn concentrations were analyzed by high-resolution inductively coupled plasma mass spectrometry. Concentrations of Mn were significantly higher in ALS CSF (median 5.67 µg/L) than in CSF from controls (median 2.08 µg/L). Also, ALS CSF Mn concentrations were higher than ALS plasma Mn concentrations (median 0.91 µg/L), suggesting transport of Mn into the central nervous system. The properties of barrier systems between blood and the brain are discussed and the possibility of Mn accumulation contributing to the relentless course of ALS is introduced.


Subject(s)
Amyotrophic Lateral Sclerosis/blood , Amyotrophic Lateral Sclerosis/cerebrospinal fluid , Manganese/blood , Manganese/cerebrospinal fluid , Aged , Aged, 80 and over , Female , Humans , Male , Mass Spectrometry , Middle Aged , Quality Control
7.
Brain Imaging Behav ; 5(3): 181-8, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21637990

ABSTRACT

This study further investigates the influence of temporarily disrupting the blood-brain barrier (BBB) on the level of manganese used in AIM fMRI other than the recognized function of allowing that substance to enter into the activated brain regions more effectively during the BBB opening. We injected manganese into Wistar rats through ICA following the disruption of BBB with mannitol in a functional MRI test of the visual cortex. Through comparing MRI signal intensity and manganese contents in the visual cortex of rats received visual stimuli of unequal degree after the restoration of BBB, we found that the signal in the visual cortex could be further enhanced on T1WI given visual stimulation after the restoration of BBB. Temporary BBB disruption has an additional advantage in allowing Mn(2+) to enter the CSF or brain for later transference to the activated brain area. So the dosage of manganese in AIM fMRI could be minimized by extending the stimulus.


Subject(s)
Blood-Brain Barrier/physiology , Magnetic Resonance Imaging/methods , Manganese/physiology , Animals , Data Interpretation, Statistical , Diuretics/pharmacology , Image Enhancement , Image Processing, Computer-Assisted , Male , Manganese/cerebrospinal fluid , Manganese/metabolism , Mannitol/pharmacology , Photic Stimulation , Rats , Rats, Wistar , Visual Cortex/physiology , Visual Fields
8.
J Neurochem ; 117(4): 747-56, 2011 May.
Article in English | MEDLINE | ID: mdl-21395586

ABSTRACT

Manganese is an essential trace element, and a contrast agent of potential interest for brain magnetic resonance imaging. Brain overexposure to manganese, however induces a neurodegenerative syndrome. Imaging data suggest that manganese appearance into the CSF precedes its accumulation into the cerebral parenchyma. We therefore investigated manganese uptake and transport at the blood-CSF barrier. Like lead, the non protein-bound divalent manganese accumulated into the rat choroid plexus. The metal accumulation was especially high in developing animals. Using a differentiated cellular model of the blood-CSF barrier, we demonstrated that manganese crosses the choroid plexus epithelium by a concentrating, unidirectional blood-to-CSF transport mechanism. This transport was inhibited by calcium, which is also transported into the CSF against its concentration gradient. The permeability barrier function towards lipid-insoluble compound and the organic anion transport property of the blood-brain interface were affected by exposure of the blood-facing membrane of choroidal cells to micromolar concentrations of manganese, but its antioxidant capacity was not. The unidirectional transport of manganese across the choroid plexus provides the anatomo-functional basis linking the systemic exposure to manganese with the spreading pattern of manganese accumulation observed in brain imaging, and explains the polarized sensitivity of choroidal epithelial cells to manganese toxicity.


Subject(s)
Brain/metabolism , Manganese/cerebrospinal fluid , Manganese/metabolism , Animals , Biological Transport, Active , Blood-Brain Barrier , Calcium/metabolism , Calcium/pharmacology , Cell Membrane Permeability , Cells, Cultured , Choroid Plexus/metabolism , Cysteine/metabolism , Dinoprostone/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Glutathione/metabolism , Indicators and Reagents , Male , Manganese/blood , Metals/metabolism , Rats , Rats, Sprague-Dawley , Sucrose/metabolism , Tight Junctions/drug effects , Tight Junctions/metabolism
9.
J Trace Elem Med Biol ; 25 Suppl 1: S45-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21146970

ABSTRACT

The aim of this study is to analyze the variation of the elements (Ca, Mg, Cu, Fe, Zn and Mn) in normal and pathological CSF and develop a classification basing on the increases in cells and proteins and taking into account these variations. A total of 173 cerebrospinal fluids were analyzed. Of these, 37 fulfilled the criteria of normality and, after clinical exploration, were considered to be healthy (control group). The remaining 136 CSFs (pathological group) belonged to people for whom some neurological pathology had been observed in the clinical exploration and whose CSF analysis presented some abnormality. CSF was extracted by puncture in the lumbar cistern. The analysis of metals was performed by atomic absorption spectrophotometry. The statistical values (mean±standard deviation) obtained for each element analyzed in control group were as follows: Ca (mg/dL): 4.95±0.70; Mg (mg/dL): 2.74±0.10; Cu (µg/dL): 15.70±13.50; Fe (µg/dL): 13.10±3.60; Zn (µg/dL): 17.40±9.50 and Mn (µg/dL): 2.50±0.70. In the pathological CSFs, significant increases were found (p<0.050) in relation to the control group for Ca, Cu, Fe, Zn and Mn in groups with an increase of both cells and proteins. A significant decrease of Mg (p<0.050) was found in the groups with cell and protein increases. Given the results obtained in the different subgroups of the proposed classification, we conclude that it is necessary to further categorize the patients' diagnostics in the different subgroups. This would help to validate the classification.


Subject(s)
Calcium/cerebrospinal fluid , Magnesium/cerebrospinal fluid , Trace Elements/cerebrospinal fluid , Adult , Aged , Case-Control Studies , Copper/cerebrospinal fluid , Female , Humans , Iron/cerebrospinal fluid , Male , Manganese/cerebrospinal fluid , Middle Aged , Zinc/cerebrospinal fluid
10.
Article in Chinese | MEDLINE | ID: mdl-20635692

ABSTRACT

OBJECTIVE: To explore the biomarkers of manganese exposure by measuring the manganese (Mn) and iron (Fe) level as well as the mRNA change of Hepcidin, divalent metal-ion transporter-1 (DMT1) and Parkin-2, one of genes related to Parkinson disease in body fluid and brain tissues of rat. METHODS: Male Sprague-Dawley rats were administered (i.p) either MnCl2 solution (6 mg Mn/kg) or the same volume saline, 5 times per week and for 4 weeks. Graphic furnace Atom Absorption Spectrum (AAS) was applied to measure the concentration of Mn and Fe in brain tissue and body fluids. Meanwhile Hepcidin, DMT1 and Parkin-2 mRNA expression were detected by real-time RT-PCR. RESULTS: Mn concentration in erythrocytes of rats was the 86.9 folds of that in control; No significant change was found in plasma. However the trend and range of Mn increase in cerebrospinal fluid (CSF) was the same as that in brain tissue including striatum, cortex, hippocampus and choroid plexus. Meanwhile Fe concentration in brain tissue of Mn exposed rats was also higher than that of control, whose trend was as same as that in CSF. However iron concentration in plasma decreased. The real-time RT-PCR data also showed that Hepcidin mRNA expression in Mn-exposed rat decreased 56% in blood, which was in line with its expression in cortex(67%). Similarly, Parkin-2 mRNA expression decreased both in blood (42%) and in striatum. However DMT1 mRNA expression increase 38% in striatum of Mn-exposed rats but decreased in blood. CONCLUSION: Hepcidin and Parkin-2 mRNA expression in blood might be serves as the effective biomarkers following manganese exposure, certainly which needs to be further explored.


Subject(s)
Antimicrobial Cationic Peptides/metabolism , Cation Transport Proteins/metabolism , Environmental Exposure , Manganese/blood , Manganese/cerebrospinal fluid , Ubiquitin-Protein Ligases/metabolism , Animals , Antimicrobial Cationic Peptides/genetics , Cation Transport Proteins/genetics , Corpus Striatum/metabolism , Gene Expression Regulation , Hepcidins , Iron/blood , Iron/cerebrospinal fluid , Male , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Ubiquitin-Protein Ligases/genetics
11.
Neurobiol Aging ; 30(7): 1069-77, 2009 Jul.
Article in English | MEDLINE | ID: mdl-18068270

ABSTRACT

Abnormal interaction of beta-amyloid 42 (Abeta42) with copper, zinc and iron induce peptide aggregation and oxidation in Alzheimer's disease (AD). However, in health, Abeta degradation is mediated by extracellular metalloproteinases, neprilysin, insulin degrading enzyme (IDE) and matrix metalloproteinases. We investigated the relationship between levels of Abeta and biological metals in CSF. We assayed CSF copper, zinc, other metals and Abeta42 in ventricular autopsy samples of Japanese American men (N=131) from the population-based Honolulu Asia Aging Study. There was a significant inverse correlation of CSF Abeta42 with copper, zinc, iron, manganese and chromium. The association was particularly strong in the subgroup with high levels of both zinc and copper. Selenium and aluminum levels were not associated to CSF Abeta42. In vitro, the degradation of synthetic Abeta substrate added to CSF was markedly accelerated by low levels (2microM) of exogenous zinc and copper. While excessive interaction with copper and zinc may induce neocortical Abeta precipitation in AD, soluble Abeta degradation is normally promoted by physiological copper and zinc concentrations.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Amyloid beta-Peptides/cerebrospinal fluid , Brain/metabolism , Cerebrospinal Fluid/metabolism , Copper/cerebrospinal fluid , Zinc/cerebrospinal fluid , Aged , Aged, 80 and over , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/analysis , Asian , Brain/physiopathology , Brain Chemistry/physiology , Chromium/analysis , Chromium/cerebrospinal fluid , Cohort Studies , Copper/analysis , Humans , Iron/analysis , Iron/cerebrospinal fluid , Male , Manganese/analysis , Manganese/cerebrospinal fluid , Peptide Fragments/analysis , Peptide Fragments/cerebrospinal fluid , Zinc/analysis
12.
Neurobiol Aging ; 30(8): 1265-71, 2009 Aug.
Article in English | MEDLINE | ID: mdl-18191875

ABSTRACT

Accumulating evidence implicates a role for altered metal homeostasis in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, few investigations have addressed this issue in dementia with Lewy bodies (DLB). The aim of the present study was to investigate metal concentrations in cerebrospinal fluid (CSF) and plasma from patients with DLB and other neurodegenerative disorders. To that end, CSF and plasma samples were collected from 29 patients with DLB, 174 patients with AD, 90 patients with AD with minor vascular components, and 51 healthy volunteers. Total concentrations of Mg, Ca, Mn, Fe, Cu, Zn, Rb, Sr, and Cs were determined using mass spectrometry. Patients with DLB had elevated Ca and Mg levels in CSF and Mg levels in plasma as compared to all other groups (p<0.001). Furthermore, a combination of CSF-Mg and CSF-Ca could distinguish DLB from AD with a sensitivity of 93% and a specificity of 85%. Cu levels in both CSF and plasma tended to be higher in DLB compared to the other groups, but these trends failed to reach significance after correction for multiple comparisons. Mn, Fe, Zn, Rb, and Sr concentration in CSF or plasma were similar in all groups. The observed elevations of CSF-Mg, CSF-Ca and CSF-Cu may contribute to or be associated with the neurodegenerative process in DLB. Furthermore, determination of CSF-Mg and CSF-Ca concentration may be a valuable tool in distinguishing DLB from AD.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Calcium/cerebrospinal fluid , Lewy Body Disease/cerebrospinal fluid , Magnesium/cerebrospinal fluid , Aged , Aged, 80 and over , Alzheimer Disease/blood , Analysis of Variance , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Calcium/blood , Cesium/blood , Cesium/cerebrospinal fluid , Copper/blood , Copper/cerebrospinal fluid , Female , Humans , Iron/blood , Iron/cerebrospinal fluid , Lewy Body Disease/blood , Magnesium/blood , Male , Manganese/blood , Manganese/cerebrospinal fluid , Mass Spectrometry , Middle Aged , ROC Curve , Rubidium/blood , Rubidium/cerebrospinal fluid , Sensitivity and Specificity , Strontium/blood , Strontium/cerebrospinal fluid , Zinc/blood , Zinc/cerebrospinal fluid
13.
Anal Chim Acta ; 627(2): 258-69, 2008 Oct 10.
Article in English | MEDLINE | ID: mdl-18809082

ABSTRACT

Neurodegenerative diseases like Alzheimer's disease and Parkinson's disease are gaining increasing relevance in our aging society. However, the complex multifactorial mechanisms of these diseases are not sufficiently understood yet. Several studies indicate that metal ions play an important role in the promotion of these diseases. Consequently, the transport pathways of metals and their species to the brain are of special interest. Following oral or inhalative uptake metals are absorbed and distributed via the blood stream in the body. Transport into the brain requires crossing of the neural barriers. Our study focuses on the investigation of the permeability of the blood-cerebrospinal fluid (CSF)-barrier for selected metals (Mn, Fe, Cu, Zn, Mg and Ca). For the first time paired human serum and CSF samples obtained from a neurological department were characterised for total metal concentrations and metal species. For CSF few data are available in the literature on total metal contents and applications of element speciation analysis in CSF samples are rare. In our study mean CSF/serum ratios (n=29) were 0.7 for Mn, 0.02 for Fe, 0.02 for Cu, 0.03 for Zn, 1.3 for Mg and 0.5 for Ca. Size exclusion chromatography (SEC) online with inductively coupled plasma mass spectrometry was further developed for the size characterisation of the metal species in CSF and serum with limits of detection of 0.4microgL(-1) for Fe, 0.01microgL(-1) for Mn, 0.2microgL(-1) for Cu, 0.2microgL(-1) for Zn, 0.6microgL(-1) for Mg and 3.8microgL(-1) for Ca in the eluate from the HPLC column. Apart from Mn the application of this technique has not been published for metal speciation in CSF, yet. In the case of some Mn species it turned out that methanol, which was contained in the mobile phase of a SEC method previously published from our group on qualitative characterisation of Mn species, was interfering with the quantification. The modified method developed in this work (with NaCl but without methanol in the mobile phase; use of internal standard) allowed reliable quantification. The results clearly indicate changes in the metal species pattern due to different permeation behaviour at the blood-CSF-barrier. As part of the method validation the relative stability of complexes of albumin, transferrin and citrate with Mn, Fe, Cu and Zn was investigated.


Subject(s)
Chromatography, Gel/methods , Mass Spectrometry/methods , Metals/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Blood-Brain Barrier/metabolism , Calcium/blood , Calcium/cerebrospinal fluid , Calcium/chemistry , Copper/blood , Copper/cerebrospinal fluid , Copper/chemistry , Female , Humans , Iron/blood , Iron/cerebrospinal fluid , Iron/chemistry , Magnesium/blood , Magnesium/cerebrospinal fluid , Magnesium/chemistry , Male , Manganese/blood , Manganese/cerebrospinal fluid , Manganese/chemistry , Metals/blood , Metals/cerebrospinal fluid , Middle Aged , Permeability , Zinc/blood , Zinc/cerebrospinal fluid , Zinc/chemistry
14.
Brain Res ; 1198: 160-70, 2008 Mar 10.
Article in English | MEDLINE | ID: mdl-18243167

ABSTRACT

Manganese overexposure in non-human primates and humans causes a neurodegenerative disorder called manganism thought to be related to an accumulation of the metal in the basal ganglia. Here, we assess changes in the concentration of manganese in regions of the brain of a non-human primate (the common marmoset, Callithrix jacchus) following four systemic injections of 30 mg/kg MnCl2 H2O in the tail vein using T1-weighted magnetic resonance imaging (MRI) and compare these to changes in the rat following the same exposure route and dose. The doses were spaced 48 h apart and we imaged the animals 48 h after the final dose. We find that marmosets have significantly larger T1-weighted image enhancements in regions of the brain compared to rats, notably in the basal ganglia and the visual cortex. To confirm this difference across species reflects actual differences in manganese concentrations and not variations in the MRI properties of manganese, we measured the longitudinal relaxivity of manganese (chi1) in the in vivo brain and found no significant species' difference. The high manganese uptake in the marmoset basal ganglia and visual cortex can be explained by CSF-brain transport from the large lateral ventricles and we confirm this route of uptake with time-course MRI during a tail-vein infusion of manganese. There is also high uptake in the substructures of the hippocampus that are adjacent to the ventricles. The large manganese accumulation in these structures on overexposure may be common to all primates, including humans.


Subject(s)
Brain/drug effects , Brain/metabolism , Callithrix/metabolism , Manganese Poisoning/metabolism , Manganese/cerebrospinal fluid , Manganese/toxicity , Animals , Brain/anatomy & histology , Brain Chemistry/drug effects , Brain Chemistry/physiology , Brain Mapping , Callithrix/anatomy & histology , Cerebrospinal Fluid/drug effects , Cerebrospinal Fluid/metabolism , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Injections, Intravenous , Lateral Ventricles/drug effects , Lateral Ventricles/metabolism , Magnetic Resonance Imaging/methods , Male , Manganese/pharmacokinetics , Manganese Poisoning/physiopathology , Rats , Rats, Sprague-Dawley , Rodentia/metabolism , Species Specificity
15.
J Trace Elem Med Biol ; 21 Suppl 1: 4-9, 2007.
Article in English | MEDLINE | ID: mdl-18039486

ABSTRACT

Manganese (Mn) at high concentrations can have adverse effects on health, mainly because of its toxicity to the central nervous system. Health impacts of Mn are known mostly from occupational health studies, but the exact mechanisms how Mn, being bound to transferrin (TF) in the blood, enters the brain--are unknown. Mn speciation at the neural barriers can help to obtain more information about the pathways and carriers. This paper summarizes investigations on the size distribution of Mn carriers (e.g. proteins, peptides, carbonic acids) in serum before the neural barriers and in cerebrospinal fluid (CSF) behind them as a first characterization step of the Mn carriers being involved in moving Mn across the neural barriers. Further identification of Mn-species in CSF was successfully achieved by CZE-inductively coupled plasma (ICP)-dynamic reaction cell (DRC)-mass spectrometry (MS). Serum samples showed Mn mean concentrations of 1.7+/-0.8 microg L(-1). The size distribution of Mn-carriers showed a main peak in the TF/albumin size fitting to the known physiological ligands. However, also an increasing Mn peak at 700 Da with increasing total Mn concentration was seen. Samples of CSF showed Mn mean concentrations of 2.6 microg L(-1)=48 nM. In CSF Mn was found to be mostly bound to low-molecular-mass (LMM)-Mn carriers in the range of 640-680 Da. This is similar to the LMM compound in serum and to Mn-citrate complexes suggested to be present in body fluids. Citrate concentration was 573 microM, thus being in huge excess compared to Mn. CSF was further analyzed by CZE-ICP-DRC-MS. Several Mn-species were monitored and mostly identified. The most abundant Mn-species was Mn-citrate at a concentration of around 0.7 microg Mn L(-1).


Subject(s)
Manganese/blood , Manganese/cerebrospinal fluid , Chromatography, Gel , Electrophoresis, Capillary , Humans , Mass Spectrometry
16.
Brain Res ; 1174: 136-42, 2007 Oct 12.
Article in English | MEDLINE | ID: mdl-17868660

ABSTRACT

A method to study the protein binding patterns of trace elements in human cerebrospinal fluid (CSF) is described. Proteins in CSF samples were separated by size exclusion chromatography combined with high performance liquid chromatography (SEC-HPLC). The column was calibrated to separate proteins in the molecular weight range 6-70 kDa. Fractions were then analyzed off-line for trace elements using high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). We were able to accurately determine more than 10 elements of clinical interest in the CSF fractions. Results are presented for Cd, Mn, Fe, Pb, Cu and Zn. The total concentrations of 16 trace elements in human plasma and CSF are also presented. The method was able to differentiate the relative contribution of metallothionein and other proteins towards metal binding in human CSF.


Subject(s)
Chromatography, High Pressure Liquid/methods , Chromatography, High Pressure Liquid/standards , Metallothionein/cerebrospinal fluid , Trace Elements/cerebrospinal fluid , Adult , Cadmium/cerebrospinal fluid , Calibration , Copper/cerebrospinal fluid , Female , Humans , Iron/cerebrospinal fluid , Lead/cerebrospinal fluid , Male , Manganese/cerebrospinal fluid , Metallothionein/chemistry , Middle Aged , Molecular Weight , Particle Size , Quality Control , Reproducibility of Results , Zinc/cerebrospinal fluid
17.
Electrophoresis ; 28(9): 1380-6, 2007 May.
Article in English | MEDLINE | ID: mdl-17377947

ABSTRACT

The neurotoxic effects of manganese (Mn) at elevated concentrations are well known. This raises the question, which of the Mn species can cross neural barriers and appear in cerebrospinal fluid (CSF). CSF is the last matrix in a living human organism available for analysis before a compound reaches the brain cells and therefore it is assumed to reflect best the internal exposure of brain tissue to Mn species. A previously developed CE method was modified for separation of albumin, histidine, tyrosine, cystine, fumarate, malate, inorganic Mn, oxalacetate, alpha-keto-glutarate, nicotinamide-dinucleotide (NAD), citrate, adenosine, glutathione, and glutamine. These compounds are supposed in the literature to act as potential Mn carriers. In a first attempt, these compounds were analyzed by CZE-UV to check whether they are present in CSF. The CZE-UV method was simpler than the coupled CZE-inductively coupled plasma (ICP)-dynamic reaction cell (DRC)-MS method and it was therefore chosen to obtain a first overview information. In a second step, the coupled method (CZE-ICP-DRC-MS) was used to analyze, in detail, which of the compounds found in CSF by CZE-UV were actually bound to Mn. Finally, 13 Mn species were monitored in CSF samples, most of them being identified: Mn-histidine, Mn-fumarate, Mn-malate, inorganic Mn, Mn-oxalacetate, Mn-alpha-keto glutarate, Mn-carrying NAD, Mn-citrate and Mn-adenosine. By far the most abundant Mn species was Mn-citrate showing a concentration of 0.7 +/- 0.13 microg Mn/L. Interestingly, several other Mn species can be related to the citric acid cycle.


Subject(s)
Electrophoresis, Capillary/methods , Manganese Compounds/cerebrospinal fluid , Manganese Compounds/chemistry , Manganese/cerebrospinal fluid , Mass Spectrometry/methods , Citrates/cerebrospinal fluid , Electrophoresis, Capillary/instrumentation , Humans , Manganese Compounds/isolation & purification , Mass Spectrometry/instrumentation , Reference Standards , Reproducibility of Results
18.
Am J Kidney Dis ; 46(4): 749-53, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16183431

ABSTRACT

We report a rare case of manganese (Mn)-induced parkinsonism in a patient on maintenance hemodialysis therapy who complained of gait disturbance and dysarthria. His symptoms and abnormal magnetic resonance imaging (MRI) findings of the brain were thought to be caused, at least in part, by long-term ingestion of a health supplement (Chlorella extract) that contained 1.7 mg of Mn in the usual daily dose. Elevated serum and cerebrospinal fluid Mn levels were detected, and brain MRI showed areas of abnormal intensity in the bilateral basal ganglia (low intensity on T1-weighted images and high intensity on T2-weighted images). Edetic acid infusion therapy dramatically improved the MRI abnormalities, after which his symptoms gradually improved 4 months later.


Subject(s)
Apiaceae/chemistry , Chlorella/chemistry , Dietary Supplements/adverse effects , Manganese/adverse effects , Parkinson Disease, Secondary/chemically induced , Plant Preparations/adverse effects , Renal Dialysis , Basal Ganglia/pathology , Chelating Agents/therapeutic use , Chelation Therapy , Diabetic Nephropathies/complications , Diabetic Nephropathies/therapy , Dysarthria/chemically induced , Edetic Acid/therapeutic use , Gait Disorders, Neurologic/chemically induced , Handwriting , Humans , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/therapy , Magnetic Resonance Imaging , Male , Manganese/blood , Manganese/cerebrospinal fluid , Middle Aged , Parkinson Disease, Secondary/complications , Parkinson Disease, Secondary/pathology , Plant Preparations/chemistry
19.
Biol Trace Elem Res ; 93(1-3): 1-8, 2003.
Article in English | MEDLINE | ID: mdl-12835484

ABSTRACT

The concentrations of manganese, copper, and zinc in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and patients with no known neurological disease (control group) were measured. Manganese and copper levels were determined by two different analytical methods: atomic absorption spectrometry (AAS) and high-resolution inductively coupled plasma-mass spectrometry (HR-ICP-MS), whereas zinc levels were determined by HR-ICP-MS only. Manganese levels (mean+/-SEM) were significantly decreased in the CSF of MS patients (1.07+/-0.13 microg/L, ICP-MS; 1.08+/-0.11 microg/L, AAS) compared to the levels in the control group (1.78+/-0.26 microg/L, ICP-MS; 1.51+/-0.17 microg/L, AAS). Copper levels were significantly elevated in the CSF of MS patients (10.90+/-1.11 microg/L; ICP-MS, 11.53+/-0.83 microg/L, AAS) compared to the levels in the control group (8.67+/-0.49 microg/L, ICP-MS; 9.10+/-0.62 microg/L, AAS). There were no significant differences between the CSF zinc levels of MS and control patients. The physiological basis for the differences in manganese and copper concentrations between MS patients and controls is unknown, but could be related to alterations in the manganese- containing enzyme glutamine synthetase and the copper-containing enzyme cytochrome oxidase.


Subject(s)
Copper/cerebrospinal fluid , Manganese/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Zinc/cerebrospinal fluid , Female , Humans , Male , Spectrophotometry, Atomic
20.
Bioelectromagnetics ; 20(6): 358-64, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10453063

ABSTRACT

Eight multiparous, nonlactating pregnant Holstein cows (at 198 +/- 35 days of gestation and weighing 608 + 24 kg) and seven nonlactating nonpregnant ovariectomized heifers (weighing 370 + 29 kg) were confined to wooden metabolism crates in an electric and magnetic field chamber. Subarachnoidal catheters were inserted before the activation of the electric and magnetic fields. For 30 days, cows and heifers were continuously exposed in separate trials to electric and magnetic fields (60 Hz, 10 kV/m, and 30 microT). Blood plasma and cerebrospinal fluid samples were collected for 3 consecutive days before the exposure period, the last 3 days of the exposure period, and for 3 days starting 5 days after the exposure period. Concentrations of Ca, Mg, Cu, Zn, Fe, Mn, Na, P, and K in blood plasma and cerebrospinal fluid were determined. Exposure to electric and magnetic fields resulted in decreased concentrations of Mg in blood plasma and in increased concentrations of Ca and P and decreased concentrations of Fe and Mn in cerebrospinal fluid.


Subject(s)
Cattle/blood , Cattle/cerebrospinal fluid , Electromagnetic Fields/adverse effects , Trace Elements/blood , Trace Elements/cerebrospinal fluid , Animals , Calcium/blood , Calcium/cerebrospinal fluid , Female , Iron/blood , Iron/cerebrospinal fluid , Magnesium/blood , Magnesium/cerebrospinal fluid , Manganese/blood , Manganese/cerebrospinal fluid , Phosphorus/blood , Phosphorus/cerebrospinal fluid , Pregnancy
SELECTION OF CITATIONS
SEARCH DETAIL
...