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.
Germinal matrix haemorrhage (GMH), caused by rupturing blood vessels in the germinal matrix, is a prevalent driver of preterm brain injuries and death. Our group recently developed a model simulating GMH using intrastriatal injections of collagenase in 5-day-old rats, which corresponds to the brain development of human preterm infants. This study aimed to define changes to the blood-brain barrier (BBB) and to evaluate BBB proteins as biomarkers in this GMH model. Regional BBB functions were investigated using blood to brain 14C-sucrose uptake as well as using biotinylated BBB tracers. Blood plasma and cerebrospinal fluids were collected at various times after GMH and analysed with ELISA for OCLN and CLDN5. The immunoreactivity of BBB proteins was assessed in brain sections. Tracer experiments showed that GMH produced a defined region surrounding the hematoma where many vessels lost their integrity. This region expanded for at least 6 h following GMH, thereafter resolution of both hematoma and re-establishment of BBB function occurred. The sucrose experiment indicated that regions somewhat more distant to the hematoma also exhibited BBB dysfunction; however, BBB function was normalised within 5 days of GMH. This shows that GMH leads to a temporal dysfunction in the BBB that may be important in pathological processes as well as in connection to therapeutic interventions. We detected an increase of tight-junction proteins in both CSF and plasma after GMH making them potential biomarkers for GMH.
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 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 24h post- hypoxia/ischemia. Simultaneously, we detected early increase in blood-brain barrier-permeability at 6 and 24h 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.
Introduction and Objectives Using existing transthoracic echocardiographic indices to quantify left ventricular wall motion abnormalities (WMAs) can be difficult due to the variations in the location of the abnormalities within the left ventricle, the quality of examinations, and the inter‐/intra‐observer variability of available indices. This study aimed to evaluate a new approach for measuring the extent of WMA by calculating the percentage of abnormal wall motion and comparing it to the wall motion score index (WMSI). The study also sought to assess inter‐ and intra‐observer variability. Methods The study included 140 echocardiograms from 54 patients presenting with ST‐elevation myocardial infarction or Takotsubo syndrome. All patients underwent an echocardiographic examination according to a standard protocol and the images were used to measure the extent of akinesia (proportion akinesia, PrA), akinesia and hypokinesia (proportion akinesia/hypokinesia, PrAH), and WMSI. The inter‐observer variability between the two operators was analyzed. The intra‐observer analysis was performed by one observer using the same images at least 1 month after the first measurement. The agreement was analyzed using the Pearson correlation coefficient and Bland‐Altman plots. Results Inter‐ and intra‐observer variability for PrA and PrAH were low and comparable to those for WMSI. Conclusion PrA and PrAH are reliable and reproducible echocardiographic methods for the evaluation of left ventricular wall motion.
BackgroundNeonatal hypoxia-ischemia often leads to lifelong disabilities with limited treatments currently available. The brain vasculature is an important factor in many neonatal brain pathologies but there is a lack of diagnostic tools to evaluate the brain vascular health of neonates in a clinical setting. Measurement of blood-brain barrier tight-junction 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-1) in both blood plasma and cerebrospinal fluid (CSF) as well as blood-brain barrier function were measured in a clinically relevant hypoxia/ischemia model in neonatal rats.ResultsTemporally acute elevated levels of occludin and claudin-5 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 24h post- hypoxia/ischemia. Simultaneously, we detected early increase in blood-brain barrier-permeability at 6 and 24h 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 health and as a tool for risk assessment of neonatal brain injuries.
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