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

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.

• Authors: E Axel Andersson, Carina Mallard, C Joakim Ek
• Journal: Fluids and barriers of the CNS (Fluids Barriers CNS) Vol. 18 Issue 1 Pg. 7 (Feb 10 2021) ISSN: 2045-8118 [Electronic] England
• PMID: 33568200 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Claudin-5
• Occludin
• Zonula Occludens-1 Protein

Topics

• Animals
• Biomarkers (blood, cerebrospinal fluid, metabolism)
• Blood-Brain Barrier (metabolism)
• Claudin-5 (blood, cerebrospinal fluid, metabolism)
• Disease Models, Animal
• Female
• Hypoxia-Ischemia, Brain (blood, cerebrospinal fluid, metabolism)
• Male
• Occludin (blood, cerebrospinal fluid, metabolism)
• Rats
• Rats, Wistar
• Zonula Occludens-1 Protein (blood, cerebrospinal fluid, metabolism)