期刊
CELLS
卷 10, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/cells10071677
关键词
germinal matrix haemorrhage; blood-brain barrier; neonatal brain; tight-junctions; preterm
类别
资金
- Rune and Ulla Amlovs Foundation
- Herbert and Karin Jacobsons Foundation
- Hasselblad Foundation
- Ake Wibergs Foundation [M19-0660]
- Swedish Research Council [VR-2017-01409]
- Ahlen Foundation
- Public Health Service at the Sahlgrenska University Hospital [ALFGBG-722491]
- Swedish Brain Foundation [FO2019-0270]
- Swedish Medical Research Council (VR) [2019-01320]
- Swedish Governmental Grant to Researchers at University Hospitals [ALFGBG-718591]
- Brain Foundation [2015-0004]
- EU [874721]
- ERA-NET [0755101]
- Cerebral Palsy Alliance Australia Foundation
- Stroke-Riksforbundet Foundation
- Wilhelm and Martina Lundgren Foundation
- Vinnova [2019-01320] Funding Source: Vinnova
- Swedish Research Council [2019-01320] Funding Source: Swedish Research Council
The study investigated the impact of GMH on the BBB using a rat model, showing that GMH causes temporary dysfunction in the BBB that normalizes within 5 days. Tight-junction proteins were identified as potential biomarkers for GMH.
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 C-14-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据