title: Speciation analysis of selected metals and determination of their total contents in paired serum and cerebrospinal fluid samples: An approach to investigate the permeability of the human blood-cerebrospinal fluid-barrier.
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.
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Ecological Chemistry, Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany. volker.nischwitz@helmholtz-muenchen.de
authors.forename: Volker
authors.initials: V
authors.lastname: Nischwitz
authors.forename: Achim
authors.initials: A
authors.lastname: Berthele
authors.forename: Bernhard
authors.initials: B
authors.lastname: Michalke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001812:Blood-Brain Barrier / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry; D002850:Chromatography, Gel / Q000379:methods*; D003300:Copper / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry; D008274:Magnesium / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry; D008297:Male; D008345:Manganese / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D008670:Metals / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D008875:Middle Aged; D010539:Permeability; D015032:Zinc / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry
chemical_list: D008670:Metals; D008345:Manganese; D003300:Copper; D007501:Iron; D008274:Magnesium; D015032:Zinc; D002118:Calcium