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Fluids and Barriers of the CNS
Published in: Fluids and Barriers of the CNS 1/2021

Open Access 01-12-2021 | Biomarkers | Research

Circulating tight-junction proteins are potential biomarkers for blood–brain barrier function in a model of neonatal hypoxic/ischemic brain injury

Authors: E. Axel Andersson, Carina Mallard, C. Joakim Ek

Published in: Fluids and Barriers of the CNS | Issue 1/2021

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Abstract

Background

Neonatal encephalopathy often leads to lifelong disabilities with limited treatments currently available. The brain vasculature is an important factor in many neonatal neurological disorders but there is a lack of diagnostic tools to evaluate the brain vascular dysfunction of neonates in the clinical setting. Measurement of blood–brain barrier tight-junction (TJ) proteins have shown promise as biomarkers for brain injury in the adult. Here we tested the biomarker potential of tight-junctions in the context of neonatal brain injury.

Methods

The levels of TJ-proteins (occluding, claudin-5, and zonula occludens protein 1) in both blood plasma and cerebrospinal fluid (CSF) as well as blood–brain barrier function via 14C-sucrose (342 Da) and Evans blue extravasation were measured in a hypoxia/ischemia brain-injury model in neonatal rats.

Results

Time-dependent changes of occludin and claudin-5 levels could be measured in blood and CSF after hypoxia/ischemia with males generally having higher levels than females. The levels of claudin-5 in CSF correlated with the severity of the brain injury at 24 h post- hypoxia/ischemia. Simultaneously, we detected early increase in blood–brain barrier-permeability at 6 and 24 h after hypoxia/ischemia.

Conclusions

Levels of circulating claudin-5 and occludin are increased after hypoxic/ischemic brain injuries and blood–brain barrier-impairment and have promise as early biomarkers for cerebral vascular dysfunction and as a tool for risk assessment of neonatal brain injuries.
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Metadata
Title
Circulating tight-junction proteins are potential biomarkers for blood–brain barrier function in a model of neonatal hypoxic/ischemic brain injury
Authors
E. Axel Andersson
Carina Mallard
C. Joakim Ek
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Biomarkers
Published in
Fluids and Barriers of the CNS / Issue 1/2021
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-021-00240-9

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