Bustelo Martín, Barkhuizen Melinda, van den Hove Daniel L A, Steinbusch Harry Wilhelm M, Bruno Martín A, Loidl C Fabián, Gavilanes Antonio W Danilo
Department of Pediatrics, Maastricht University Medical Center (MUMC), Maastricht, Netherlands.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, Netherlands.
Front Neurol. 2020 Jun 9;11:483. doi: 10.3389/fneur.2020.00483. eCollection 2020.
Placental and fetal hypoxia caused by perinatal hypoxic-ischemic events are major causes of stillbirth, neonatal morbidity, and long-term neurological sequelae among surviving neonates. Brain hypoxia and associated pathological processes such as excitotoxicity, apoptosis, necrosis, and inflammation, are associated with lasting disruptions in epigenetic control of gene expression contributing to neurological dysfunction. Recent studies have pointed to DNA (de)methylation, histone modifications, and non-coding RNAs as crucial components of hypoxic-ischemic encephalopathy (HIE). The understanding of epigenetic dysregulation in HIE is essential in the development of new clinical interventions for perinatal HIE. Here, we summarize our current understanding of epigenetic mechanisms underlying the molecular pathology of HI brain damage and its clinical implications in terms of new diagnostic, prognostic, and therapeutic tools.
围产期缺氧缺血事件导致的胎盘和胎儿缺氧是死产、新生儿发病以及存活新生儿长期神经后遗症的主要原因。脑缺氧以及相关的病理过程，如兴奋性毒性、细胞凋亡、坏死和炎症，与基因表达表观遗传控制的持续破坏有关，进而导致神经功能障碍。最近的研究指出，DNA（去）甲基化、组蛋白修饰和非编码RNA是缺氧缺血性脑病（HIE）的关键组成部分。了解HIE中的表观遗传失调对于开发围产期HIE的新临床干预措施至关重要。在此，我们总结了目前对HI脑损伤分子病理学表观遗传机制的理解及其在新的诊断、预后和治疗工具方面的临床意义。
