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Journal of Lipid Research, Vol. 44, 793-799, April 2003
Copyright © 2003 by Lipid Research, Inc.

Side chain oxidized oxysterols in cerebrospinal fluid and the integrity of blood-brain and blood-cerebrospinal fluid barriers

Valerio Leoni^2,*,, Thomas Masterman^2,, Pria Patel, Steve Meaney, Ulf Diczfalusy and Ingemar Björkhem^1,

^* Department of Experimental and Clinical Biomedical Science, University of Insubria, Varese, Italy
Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden
Division of Neurology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden

¹ To whom correspondence should be addressed. e-mail: ingemar.bjorkhem{at}hs.se

The side chain oxidized oxysterol 24S-hydroxycholesterol (24-OH-chol) is formed almost exclusively in the brain, and there is a continuous passage of this oxysterol through the circulation to the liver. 27-Hydroxycholesterol (27-OH-chol) is produced in most organs and is also taken up by the liver. The 27-OH-chol-24-OH-chol ratio is about 0.1 in the brain and about 2 in the circulation. This ratio was found to be about 0.4 in cerebrospinal fluid (CSF) of asymptomatic patients, consistent with a major contribution from the circulation in the case of 27-OH-chol. In accordance with this, we demonstrated a significant flux of deuterium labeled 27-OH-chol from plasma to the CSF in a healthy volunteer. Patients with a defective blood-brain barrier were found to have markedly increased absolute levels (up to 10-fold) of both 27-OH-chol and 24-OH-chol in CSF, with a ratio between the two sterols reaching up to 2. There was a significant positive correlation between the levels of both oxysterols in CSF and the albumin_CSF-albumin_plasma ratio. The 27-OH-chol_CSF-24-OH-chol_CSF ratio was found to be about normal in patients with active multiple sclerosis and significantly increased in patients with meningitis, polyneuropathy, or hemorrhages.

Results are discussed in relation to the possible use of 24-OH-chol_CSF as a surrogate marker of central nervous system demyelination and/or neuronal death.

Abbreviations: BBB, blood-brain barrier; CSF, cerebrospinal fluid; MS, multiple sclerosis; 24-OH-chol, 24S-hydroxycholesterol; 27-OH-chol, 27-hydroxycholesterol; Q_Alb, albumin_CSF-albumin_plasma ratio

Supplementary key words 24S-hydroxycholesterol • 27-hydroxycholesterol • neurodegeneration • demyelination

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