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Papers In Press, published online ahead of print February 1, 2003
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Department of Laboratory Medicine, Karolinska Institute, Stockholm S14186
Corresponding Author: ingemar.bjorkhem{at}hs.se
The side-chain oxidised oxysterol 24S-hydroxycholesterol is almost exclusively formed in the brain, and there is a continuous passage of this oxysterol through the circulation to the liver. 27-Hydroxycholesterol is produced in most organs and is also taken up by the liver. The 27-hydroxycholesterol:24S-hydroxycholesterol 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-hydroxycholesterol. In accordance with this we could demonstrate a significant flux of deuterium labelled 27-hydroxycholesterol 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-hydroxycholesterol and 24S-hydroxycholesterol 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 AlbuminCSF:Albuminplasma ratio. The 27-hydroxycholesterolCSF:24S-hydroxycholesterolCSF ratio was found to be about normal in patients with active multiple sclerosis and significantly increased in patients with meningitis, polyneuropathy or haemorrhage. Results are discussed in relation to the possible use of 24S-hydroxycholesterolCSF as a surrogate marker of CNS demyelination and/or neuronal death.
Revised on January 17, 2003
Accepted on January 23, 2003
Side-chain oxidised oxysterols in cerebrospinal fluid and integrity of blood-brain and blood-CSF barriers
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