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用于评估围产期脑病的血液生物标志物

Blood Biomarkers for Evaluation of Perinatal Encephalopathy.

作者信息

Graham Ernest M, Burd Irina, Everett Allen D, Northington Frances J

机构信息

Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of MedicineBaltimore, MD, USA; Neuroscience Intensive Care Nursery Program, Johns Hopkins University School of MedicineBaltimore, MD, USA.

Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of MedicineBaltimore, MD, USA; Neuroscience Intensive Care Nursery Program, Johns Hopkins University School of MedicineBaltimore, MD, USA; Department of Neurology, Johns Hopkins University School of MedicineBaltimore, MD, USA; Integrated Research Center for Fetal Medicine, Johns Hopkins University School of MedicineBaltimore, MD, USA.

出版信息

Front Pharmacol. 2016 Jul 13;7:196. doi: 10.3389/fphar.2016.00196. eCollection 2016.

Abstract

Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products, and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the "liquid brain biopsy." A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

摘要

近期关于创伤后脑损伤识别的研究表明,有许多可能的血液生物标志物有助于识别患有脑病的胎儿和新生儿。创伤性脑损伤与围产期缺氧缺血性脑病有许多共同特征。创伤有缺氧成分,中重度创伤性脑损伤的首要生理后果之一是呼吸暂停。创伤和缺氧缺血引发兴奋性毒性级联反应和自由基损伤,随后是炎症级联反应,对神经元、胶质细胞和白质造成损伤。创伤性脑损伤和围产期脑病都存在兴奋性氨基酸增加、脂质过氧化产物以及微小RNA和炎症标志物的改变。两者都会导致血脑屏障破坏,致使通常仅在中枢神经系统中发现的物质外流。脑外泌体可能是理想的生物标志物载体,因为囊泡内运输的RNA和蛋白质受到保护,不会被酶降解。评估穿过血脑屏障并在外周循环的胎儿或新生儿脑源性外泌体被称为“液体脑活检”。多种血清生物标志物可能会改进目前识别胎儿和新生儿脑损伤的不精确方法,如胎儿心率异常、胎粪、分娩时脐带血气和阿氏评分。围产期脑损伤和恢复的生物标志物定量测量可能仅在胎儿存在重大风险时才会导致手术分娩,有助于出生后进行适当治疗的分类,并衡量治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d32/4942457/bf4ec5781bec/fphar-07-00196-g0001.jpg

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