Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial

(1) Background: Bile acids, known as aids in intestinal fat digestion and as messenger molecules in serum, can be detected in cerebrospinal fluid (CSF), although the blood–brain barrier is generally an insurmountable obstacle for bile acids. The exact mechanisms of the occurrence, as well as possibl...

Full description

Bibliographic Details
Main Authors: Lars-Olav Harnisch, Sophie Neugebauer, Diana Mihaylov, Abass Eidizadeh, Bozena Zechmeister, Ilko Maier, Onnen Moerer
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/11/2947
_version_ 1797460056509251584
author Lars-Olav Harnisch
Sophie Neugebauer
Diana Mihaylov
Abass Eidizadeh
Bozena Zechmeister
Ilko Maier
Onnen Moerer
author_facet Lars-Olav Harnisch
Sophie Neugebauer
Diana Mihaylov
Abass Eidizadeh
Bozena Zechmeister
Ilko Maier
Onnen Moerer
author_sort Lars-Olav Harnisch
collection DOAJ
description (1) Background: Bile acids, known as aids in intestinal fat digestion and as messenger molecules in serum, can be detected in cerebrospinal fluid (CSF), although the blood–brain barrier is generally an insurmountable obstacle for bile acids. The exact mechanisms of the occurrence, as well as possible functions of bile acids in the central nervous system, are not precisely understood. (2) Methods: We conducted a single-center observational trial. The concentrations of 15 individual bile acids were determined using an in-house LC-MS/MS method in 54 patients with various acute and severe disorders of the central nervous system. We analyzed CSF from ventricular drainage taken within 24 h after placement, and blood samples were drawn at the same time for the presence and quantifiability of 15 individual bile acids. (3) Results: At a median time of 19.75 h after a cerebral insult, the concentration of bile acids in the CSF was minute and almost negligible. The CSF concentrations of total bile acids (TBAs) were significantly lower compared to the serum concentrations (serum 0.37 µmol/L [0.24, 0.89] vs. 0.14 µmol/L [0.05, 0.43]; <i>p</i> = 0.033). The ratio of serum-to-CSF bile acid levels calculated from the respective total concentrations were 3.10 [0.94, 14.64] for total bile acids, 3.05 for taurocholic acid, 14.30 [1.11, 27.13] for glycocholic acid, 0.0 for chenodeoxycholic acid, 2.19 for taurochenodeoxycholic acid, 1.91 [0.68, 8.64] for glycochenodeoxycholic acid and 0.77 [0.0, 13.79] for deoxycholic acid; other bile acids were not detected in the CSF. The ratio of CSF-to-serum S100 concentration was 0.01 [0.0, 0.02]. Serum total and conjugated (but not unconjugated) bilirubin levels and serum TBA levels were significantly correlated (total bilirubin <i>p</i> = 0.031 [0.023, 0.579]; conjugated bilirubin <i>p</i> = 0.001 [0.193, 0.683]; unconjugated <i>p</i> = 0.387 [−0.181, 0.426]). No correlations were found between bile acid concentrations and age, delirium, intraventricular blood volume, or outcome measured on a modified Rankin scale. (4) Conclusions: The determination of individual bile acids is feasible using the current LC-MS/MS method. The results suggest an intact blood–brain barrier in the patients studied. However, bile acids were detected in the CSF, which could have been achieved by active transport across the blood–brain barrier.
first_indexed 2024-03-09T17:00:45Z
format Article
id doaj.art-8d37d2bfd00e4cf09b48ed6b95a1ecbb
institution Directory Open Access Journal
issn 2227-9059
language English
last_indexed 2024-03-09T17:00:45Z
publishDate 2023-11-01
publisher MDPI AG
record_format Article
series Biomedicines
spelling doaj.art-8d37d2bfd00e4cf09b48ed6b95a1ecbb2023-11-24T14:30:53ZengMDPI AGBiomedicines2227-90592023-11-011111294710.3390/biomedicines11112947Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational TrialLars-Olav Harnisch0Sophie Neugebauer1Diana Mihaylov2Abass Eidizadeh3Bozena Zechmeister4Ilko Maier5Onnen Moerer6Department of Anaesthesiology, University Medical Center, University of Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, GermanyInstitute of Clinical Chemistry and Laboratory Diagnostics, University Hospital Jena, Am Klinikum 1, D-07747 Jena, GermanyInstitute of Clinical Chemistry and Laboratory Diagnostics, University Hospital Jena, Am Klinikum 1, D-07747 Jena, GermanyInterdisciplinary UMG Laboratories, University Medical Center, University of Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, GermanyInterdisciplinary UMG Laboratories, University Medical Center, University of Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, GermanyDepartment of Neurology, University Medical Center, University of Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, GermanyDepartment of Anaesthesiology, University Medical Center, University of Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, Germany(1) Background: Bile acids, known as aids in intestinal fat digestion and as messenger molecules in serum, can be detected in cerebrospinal fluid (CSF), although the blood–brain barrier is generally an insurmountable obstacle for bile acids. The exact mechanisms of the occurrence, as well as possible functions of bile acids in the central nervous system, are not precisely understood. (2) Methods: We conducted a single-center observational trial. The concentrations of 15 individual bile acids were determined using an in-house LC-MS/MS method in 54 patients with various acute and severe disorders of the central nervous system. We analyzed CSF from ventricular drainage taken within 24 h after placement, and blood samples were drawn at the same time for the presence and quantifiability of 15 individual bile acids. (3) Results: At a median time of 19.75 h after a cerebral insult, the concentration of bile acids in the CSF was minute and almost negligible. The CSF concentrations of total bile acids (TBAs) were significantly lower compared to the serum concentrations (serum 0.37 µmol/L [0.24, 0.89] vs. 0.14 µmol/L [0.05, 0.43]; <i>p</i> = 0.033). The ratio of serum-to-CSF bile acid levels calculated from the respective total concentrations were 3.10 [0.94, 14.64] for total bile acids, 3.05 for taurocholic acid, 14.30 [1.11, 27.13] for glycocholic acid, 0.0 for chenodeoxycholic acid, 2.19 for taurochenodeoxycholic acid, 1.91 [0.68, 8.64] for glycochenodeoxycholic acid and 0.77 [0.0, 13.79] for deoxycholic acid; other bile acids were not detected in the CSF. The ratio of CSF-to-serum S100 concentration was 0.01 [0.0, 0.02]. Serum total and conjugated (but not unconjugated) bilirubin levels and serum TBA levels were significantly correlated (total bilirubin <i>p</i> = 0.031 [0.023, 0.579]; conjugated bilirubin <i>p</i> = 0.001 [0.193, 0.683]; unconjugated <i>p</i> = 0.387 [−0.181, 0.426]). No correlations were found between bile acid concentrations and age, delirium, intraventricular blood volume, or outcome measured on a modified Rankin scale. (4) Conclusions: The determination of individual bile acids is feasible using the current LC-MS/MS method. The results suggest an intact blood–brain barrier in the patients studied. However, bile acids were detected in the CSF, which could have been achieved by active transport across the blood–brain barrier.https://www.mdpi.com/2227-9059/11/11/2947bile acidsblood–brain barrieradaptive responseactive transport
spellingShingle Lars-Olav Harnisch
Sophie Neugebauer
Diana Mihaylov
Abass Eidizadeh
Bozena Zechmeister
Ilko Maier
Onnen Moerer
Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial
Biomedicines
bile acids
blood–brain barrier
adaptive response
active transport
title Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial
title_full Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial
title_fullStr Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial
title_full_unstemmed Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial
title_short Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial
title_sort quantification of bile acids in cerebrospinal fluid results of an observational trial
topic bile acids
blood–brain barrier
adaptive response
active transport
url https://www.mdpi.com/2227-9059/11/11/2947
work_keys_str_mv AT larsolavharnisch quantificationofbileacidsincerebrospinalfluidresultsofanobservationaltrial
AT sophieneugebauer quantificationofbileacidsincerebrospinalfluidresultsofanobservationaltrial
AT dianamihaylov quantificationofbileacidsincerebrospinalfluidresultsofanobservationaltrial
AT abasseidizadeh quantificationofbileacidsincerebrospinalfluidresultsofanobservationaltrial
AT bozenazechmeister quantificationofbileacidsincerebrospinalfluidresultsofanobservationaltrial
AT ilkomaier quantificationofbileacidsincerebrospinalfluidresultsofanobservationaltrial
AT onnenmoerer quantificationofbileacidsincerebrospinalfluidresultsofanobservationaltrial