Clinical Implications of Epigenetic Dysregulation in Perinatal Hypoxic-Ischemic Brain Damage

Frontiers in Neurology

Melinda Barkhuizen¹  Harry Wilhelm. M. Steinbusch²  Daniel L. A. van den Hove³  Antonio W. Danilo Gavilanes⁴  Martín A. Bruno⁵  C. Fabián Loidl⁶  Martín Bustelo⁶ 

[1] 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;Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany;Facultad de Ciencias Médicas, Instituto de Investigación e Innovación de Salud Integral, Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador;Instituto de Ciencias Biomédicas, Facultad de Ciencias Médicas, Universidad Católica de Cuyo, San Juan, Argentina;Laboratorio de Neuropatología Experimental, Facultad de Medicina, Instituto de Biología Celular y Neurociencias “Prof. E. De Robertis” (IBCN), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina;

关键词: hypoxic-ischemic encephalopathy;    biomarker;    hypoxia;    ischemia;    microRNAs;    histone modifications;   

DOI  :  10.3389/fneur.2020.00483

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown