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. 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. 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. 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.

中文翻译：

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循环紧密连接蛋白是新生儿缺氧/缺血性脑损伤模型中血脑屏障功能的潜在生物标志物

新生儿脑病通常会导致终身残疾，目前可用的治疗方法有限。脑血管系统是许多新生儿神经系统疾病的重要因素，但缺乏在临床环境中评估新生儿脑血管功能障碍的诊断工具。血脑屏障紧密连接 (TJ) 蛋白的测量显示出作为成人脑损伤生物标志物的前景。在这里，我们测试了新生儿脑损伤背景下紧密连接的生物标志物潜力。血浆和脑脊液 (CSF) 中 TJ 蛋白（闭塞、密闭蛋白 5 和闭塞小带蛋白 1）的水平以及通过 14C-蔗糖（342 Da）和伊文思蓝外渗产生的血脑屏障功能是在新生大鼠的缺氧/缺血脑损伤模型中测量。可以在缺氧/缺血后在血液和脑脊液中测量 occludin 和 claudin-5 水平的时间依赖性变化，男性的水平通常高于女性。脑脊液中 claudin-5 的水平与缺氧/缺血后 24 小时脑损伤的严重程度相关。同时，我们在缺氧/缺血后 6 和 24 小时检测到血脑屏障通透性的早期增加。缺氧/缺血性脑损伤和血脑屏障受损后循环 claudin-5 和 occludin 的水平增加，有望作为脑血管功能障碍的早期生物标志物和新生儿脑损伤风险评估的工具。脑脊液中 claudin-5 的水平与缺氧/缺血后 24 小时脑损伤的严重程度相关。同时，我们在缺氧/缺血后 6 和 24 小时检测到血脑屏障通透性的早期增加。缺氧/缺血性脑损伤和血脑屏障受损后循环 claudin-5 和 occludin 的水平增加，有望作为脑血管功能障碍的早期生物标志物和新生儿脑损伤风险评估的工具。脑脊液中 claudin-5 的水平与缺氧/缺血后 24 小时脑损伤的严重程度相关。同时，我们在缺氧/缺血后 6 和 24 小时检测到血脑屏障通透性的早期增加。缺氧/缺血性脑损伤和血脑屏障受损后循环 claudin-5 和 occludin 的水平增加，有望作为脑血管功能障碍的早期生物标志物和新生儿脑损伤风险评估的工具。