# Fluorometric Nanoscale Analysis of Bilirubin and Biliverdin in Human Cerebrospinal Fluid

**Authors:** Paola Sist, Federica Tramer, Arianna Sartori, Paolo Manganotti, Sabina Passamonti

PMC · DOI: 10.1021/acschemneuro.5c00265 · ACS Chemical Neuroscience · 2025-06-25

## TL;DR

This study uses a fluorometric method to measure bilirubin and biliverdin in cerebrospinal fluid, which could help in diagnosing neurological disorders.

## Contribution

The study introduces a sensitive fluorometric method using the HUG protein for bilirubin and biliverdin quantification in CSF.

## Key findings

- Bilirubin concentrations in CSF ranged from 14 to 340 nM.
- Biliverdin concentrations ranged from 0 to 66 nM in the same samples.
- The method is suitable for routine analysis in small-scale laboratories.

## Abstract

Cerebrospinal fluid
(CSF) is a valuable source for the quantification
of soluble, brain-specific biomarkers supporting the diagnosis of
some neurological disorders, infectious diseases, and suspected subarachnoid
hemorrhage. Given the increasing need to expand the basic knowledge
of brain pathophysiology for disease biomarker discovery, we set the
goal to quantify bilirubin and biliverdin in human CSF. Their concentrations
are expected to reflect the level of brain heme catabolism, a key
pathway involved in the biological response to oxidative stress. Here,
we present the results of the CSF analysis by a specific and sensitive
fluorometric method using the recombinant fusion protein HELP-UnaG
(HUG). The concentrations of bilirubin and biliverdin in 50 human
CSF samples were in the ranges of 14–340 and 0–66 nM,
respectively. This assay can be easily implemented in small-scale
laboratories and neurological units for the routine analysis of clinical
CSF samples.

## Linked entities

- **Proteins:** CPLANE1 (ciliogenesis and planar polarity effector complex subunit 1)
- **Chemicals:** bilirubin (PubChem CID 5280352), biliverdin (PubChem CID 251)
- **Diseases:** subarachnoid hemorrhage (MONDO:0005099)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Diseases:** infectious diseases (MESH:D003141), subarachnoid hemorrhage (MESH:D013345), neurological disorders (MESH:D009461)
- **Chemicals:** Biliverdin (MESH:D001664), heme (MESH:D006418), Bilirubin (MESH:D001663)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12272545/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12272545/full.md

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Source: https://tomesphere.com/paper/PMC12272545