title: Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis.
abstract: In a recent publication [Diestel, A., O. Aktas, D. Hackel, I. Hake, S. Meier, C. S. Raine, R. Nitsch, F. Zipp, and O. Ullrich. 2003. Activation of microglial poly (ADP-ribose)-polymerase-1 by cholesterol breakdown products during neuroinflammation: a link between demyelination and neuronal damage. J. Exp. Med. 198: 1729-1740], extremely high levels of 7-oxocholesterol were reported in cerebrospinal fluid (CSF) of 11 patients with multiple sclerosis (MS) [7.4 +/- 0.3 mg/l (mean +/- SEM)]. The corresponding level of 12 subjects with other kinds of neurological diseases was reported to be 0.5 +/- 0.1 mg/l. Such high levels of 7-oxocholesterol were found to cause neuronal damage of living brain tissues. Using a highly accurate method for an assay of 7-oxocholesterol based on isotope dilution-mass spectrometry and anaerobic conditions during workup, we found that the level of 7-oxocholesterol in CSF from 29 Swedish patients with MS was only 1.2 microg/l (median, ranging from 0.4 to 4.6 microg/l), less than 1/1,000 th of the previously reported level. The level of 7-oxocholesterol in CSF from 24 Swedish control patients was 0.9 microg/l (0.3-2.3 microg/l), slightly but significantly lower than the CSF level in MS patients (P=0.002). In vitro-induced lipid peroxidation of the endogenous cholesterol in CSF increased the level of 7-oxygenated cholesterol metabolites, particularly 7-oxocholesterol, up to approximately 0.3 mg/l. These results are discussed in relation to the fact that 7-oxygenated steroids are easily artificially formed by autoxidation of cholesterol during workup procedures and analysis of sterols and oxysterols from biological samples.
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska University Hospital in Huddinge, Stockholm, Sweden.
authors.forename: Valerio
authors.initials: V
authors.lastname: Leoni
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Thomas
authors.initials: T
authors.lastname: Masterman
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D006801:Humans; D007653:Ketocholesterols / Q000134:cerebrospinal fluid*; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid*; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid; D010100:Oxygen / Q000378:metabolism; D012189:Retrospective Studies; D013261:Sterols / Q000378:metabolism; D013997:Time Factors
chemical_list: D007653:Ketocholesterols; D013261:Sterols; D002784:Cholesterol; C003001:7-ketocholesterol; D010100:Oxygen