Abstract
BackgroundNeonatal 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.MethodsThe 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.ResultsTime-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.ConclusionsLevels 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.
Highlights
Neonatal encephalopathy often leads to lifelong disabilities with limited treatments currently available
Hypoxia–ischemia (HI) Postnatal day 7 (PND7) rats were anaesthetised with isoflurane (3.5–5%, Vetmedic, Stockholm, Sweden) in a 50/50 oxygen/nitrogen mixture, placed on their backs and a small incision was made in the neck to gain access to the carotid artery
HI induced caspase‐3 activation in the injured brain hemisphere In this model of neonatal HI, the combination of left carotid artery ligation and global hypoxia produces brain injury and tissue loss in the left hemisphere [36]
Summary
Neonatal encephalopathy often leads to lifelong disabilities with limited treatments currently available. The resulting brain injuries are typically visualised by advanced imaging methods such as MRI and CT-scans [10], techniques that are both expensive and have a relatively low availability, in terms of both equipment and skilled personnel, in many countries [11]. This is important to note as it has been estimated that as many as 96% of neonates affected by NE are born in low- and middleincome countries [12]. Putative biomarkers for neuronal damage following NE would be a valuable diagnostic tool to predict long-term outcomes but has the drawback that they are usually measurable only after the injury has manifested [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
