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

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

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