Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag CIS-MS-MS and LC-ESI-MS-MS with Picolinic Derivatization: Increased Levels and Association with Disability duriReport as inadecuate




Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag CIS-MS-MS and LC-ESI-MS-MS with Picolinic Derivatization: Increased Levels and Association with Disability duri - Download this document for free, or read online. Document in PDF available to download.

Neuromyelitis optica NMO is an inflammatory demyelinating disease of the central nervous system CNS. Hydroxycholesterols OHCs, metabolites of CNS cholesterol, are involved in diverse cellular responses to inflammation and demyelination, and may also be involved in the pathogenesis of NMO. We aimed to develop a sensitive and reliable method for the quantitative analysis of three major OHCs 24S-, 25-, and 27-OHCs, and to evaluate their concentration in the cerebrospinal fluid CSF and serum of patients with NMO. The levels of the three OHCs in the serum and CSF were measured using liquid chromatography-silver ion coordination ionspray tandem mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry with picolinyl ester derivatization, respectively. The linear range was 5–250 ng-mL for 24S- and 27-OHC, and 0.5–25 ng-mL for 25-OHC in serum, and was 0.1–5 ng-mL for 24S- and 27-OHC, and 0.03–1 ng-mL for 25-OHC in CSF. Precision and accuracy were 0.5%–14.7% and 92.5%–109.7%, respectively, in serum, and were 0.8%–7.7% and 94.5%–119.2%, respectively, in CSF. Extraction recovery was 82.7%–90.7% in serum and 68.4%–105.0% in CSF. When analyzed in 26 NMO patients and 23 control patients, the 25-OHC 0.54 ± 0.96 ng-mL vs. 0.09 ± 0.04 ng-mL, p = 0.032 and 27-OHC 2.68 ± 3.18 ng-mL vs. 0.68 ± 0.25 ng-mL, p = 0.005 were increased in the CSF from NMO patients. When we measured the OHCCSF index that controls the effects of blood–brain barrier disruption on the level of OHC in the CSF, the 27-OHCCSF index was associated with disability 0.723; 95% confidence interval CI– 0.181, 0.620; p = 0.002, while the 24-OHCCSF index 0.518; 95% CI– 1.070, 38.121; p = 0.040 and 25-OHCCSF index 0.677; 95% CI– 4.313, 18.532; p = 0.004 were associated with the number of white blood cells in the CSF of NMO patients. Our results imply that OHCs in the CNS could play a role in the pathogenesis of NMO.



Author: Eunju Cha , Kang Mi Lee , Ki Duk Park, Kyung Seok Park, Kwang-Woo Lee, Sung-Min Kim , Jaeick Lee

Source: http://plos.srce.hr/



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