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Originally published In Press as doi:10.1194/jlr.M500024-JLR200 on March 1, 2005

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Journal of Lipid Research, Vol. 46, 1047-1052, May 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Crossing the barrier: net flux of 27-hydroxycholesterol into the human brain

Maura Heverin*, Steve Meaney*, Dieter Lütjohann{dagger}, Ulf Diczfalusy*, John Wahren§ and Ingemar Björkhem1,*

* Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska University Hospital, Huddinge, Sweden
{dagger} Department of Clinical Pharmacology, University of Bonn, Bonn, Germany
§ Department of Surgical Sciences, Karolinska University Hospital, Solna, Sweden

1 To whom correspondence should be addressed. e-mail: Ingemar.Bjorkhem{at}karolinska.se

Side chain oxidized oxysterols have a unique ability to traverse lipophilic membranes. We tested the hypothesis that there is a net flux of 27-hydroxycholesterol from the circulation into the brain using plasma samples collected from the internal jugular vein and an artery of healthy male volunteers. Two independent studies were performed, one in which total levels of 27-hydroxycholesterol were measured and one in which the free fraction of 27-hydroxycholesterol was measured. In the majority of subjects studied, the level of 27-hydroxycholesterol was higher in the artery than in the vein, and uptake from the circulation was calculated to be about 5 mg/24 h.

The distribution of 27-hydroxycholesterol in human brain was found to be consistent with an extracerebral origin, with a concentration gradient from the white to the gray matter

Supplementary key words blood–brain barrier • brain cholesterol • oxysterol • 24S-hydroxycholesterol


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