Abstract
We confirmed previous findings by a Japanese group that there is an accumulation of 7α-hydroxy-3-oxo-4-cholestenoic acid (7-Hoca) in human subdural hematomas. The accumulation correlated with the time from the bleeding to the sample collection. We present evidence that these accumulations are likely to be caused by the strong affinity of 7-Hoca to albumin and the marked difference between plasma and brain with respect to levels of albumin. In the circulation, 80-90% of 7-Hoca is bound to albumin with a ratio between the steroid acid and albumin of ∼1.4 ng/mg. In cerebrospinal fluid (CSF), the ratio between 7-Hoca and albumin is ∼30 ng/mg. When albumin or hemolyzed blood in a dialysis bag was exposed to CSF, there was a flux of 7-Hoca from CSF to the albumin. We suggest that the major explanation for accumulation of 7-Hoca in subdural hematoma is a flux from the brain into the hematoma due to the high affinity to albumin and the high capacity of 7-Hoca to pass biomembranes. We discuss the possibility that the markedly different ratios between 7-Hoca and albumin in circulation and brain can explain the flux of 7-Hoca from the brain into circulation against a concentration gradient.
Highlights
We confirmed previous findings by a Japanese group that there is an accumulation of 7 -hydroxy-3-oxo-4cholestenoic acid (7-Hoca) in human subdural hematomas
Our findings suggest that the strong binding of 7-Hoca to albumin and the marked difference of 7-Hoca/albumin ratio between cerebrospinal fluid (CSF) and plasma plays an important role in the above accumulations
Given the structural similarity between 7-Hoca and bile acids, with the former possessing a C27 steroid side chain instead of a C24 steroid side chain, a firm binding of this compound to albumin could be expected in the circulation
Summary
Assay of 7-Hoca and 3-oxo-cholesta-4,6-dienoic acid D4-7-Hoca was synthesized as described previously (10) and used as internal standard. CSF samples from patients with intracerebral bleedings We collected a few CSF samples containing blood from our routine laboratory at the division of clinical chemistry at the Karolinska University Hospital Huddinge (visual inspection only). This CSF corresponds to excess materials that were available 1 week after the diagnostic measurements had been performed. Incubation of artificial hematoma material in CSF Hemolyzed blood was prepared according to the method described by Moore et al (11) by snap-freezing a few milliliters of a blood pool in liquid nitrogen. Two milliliters of the hemolyzed blood was sealed in a dialysis membrane and incubated in CSF in the same way described for the albumin solution. The pools of CSF and blood were obtained from anonymous donors (waste materials from the routine laboratory)
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