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.
Highlights
In a recent publication [Diestel, A., O
Evaluation of the method To evaluate the accuracy of the method, the recovery of the oxysterols from spiked cerebrospinal fluid (CSF) samples was measured
There was no significant difference between CSF cholesterol levels in multiple sclerosis (MS) patients and controls
Summary
In a recent publication [Diestel, A., O. 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. In vitro-induced lipid peroxidation of the endogenous cholesterol in CSF increased the level of 7-oxygenated cholesterol metabolites, 7-oxocholesterol, up to ف0.3 mg/l. These results are discussed in relation to the fact that 7-oxygenated steroids are artificially formed by autoxidation of cholesterol during workup procedures and analysis of sterols and oxysterols from biological samples.—Leoni, V., D. The results are discussed in relation to the fact that 7-oxygenated steroids are artificially formed by autoxidation of cholesterol during workup procedures and analysis of sterols and oxysterols from biological samples
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