TY - JOUR
T1 - Clinical Implications of Epigenetic Dysregulation in Perinatal Hypoxic-Ischemic Brain Damage
AU - Bustelo, Martin
AU - Barkhuizen, Melinda
AU - van den Hove, Daniel L. A.
AU - Steinbusch, Harry Wilhelm M.
AU - Bruno, Martn A.
AU - Fabian Loidl, C.
AU - Danilo Gavilanes, Antonio W.
N1 - Funding Information:
Funding. This research was partially supported by the Sistema de Investigación y Desarrollo (SINDE) and the Vicerrectorado de Investigación y Posgrado of the Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador. MBu was funded by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) of Argentina and the Foundation of Pediatrics, Maastricht University Medical Center+ (MUMC+). CL was supported by Universidad de Buenos Aires (UBACyT - 20020160100150BA). All views expressed in this article are those of the authors and do not represent the views of the funding agencies.
Publisher Copyright:
© Copyright © 2020 Bustelo, Barkhuizen, van den Hove, Steinbusch, Bruno, Loidl and Gavilanes.
PY - 2020/6/9
Y1 - 2020/6/9
N2 - 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.
AB - 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.
KW - hypoxic-ischemic encephalopathy
KW - biomarker
KW - hypoxia
KW - ischemia
KW - microRNAs
KW - histone modifications
KW - DNA methylation
KW - HUMAN ENDOTHELIAL-CELLS
KW - LONG NONCODING RNAS
KW - NEONATAL BRAIN
KW - INDUCIBLE FACTOR
KW - DNA METHYLATION
KW - GENE-EXPRESSION
KW - PROVIDES NEUROPROTECTION
KW - HISTONE DEMETHYLASES
KW - HUMAN PLACENTAS
KW - DOWN-REGULATION
U2 - 10.3389/fneur.2020.00483
DO - 10.3389/fneur.2020.00483
M3 - (Systematic) Review article
C2 - 32582011
SN - 1664-2295
VL - 11
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 483
ER -