Impaired oligodendrocyte maturation in preterm infants: Potential therapeutic targets

Van Tilborg, E, Heijnen, C, Benders, M, van Bel, F, Fleiss, B, Gressens, P and Nijboer, C 2016, 'Impaired oligodendrocyte maturation in preterm infants: Potential therapeutic targets', Progress in Neurobiology, vol. 136, pp. 28-49.

Document type: Journal Article
Collection: Journal Articles

Title Impaired oligodendrocyte maturation in preterm infants: Potential therapeutic targets
Author(s) Van Tilborg, E
Heijnen, C
Benders, M
van Bel, F
Fleiss, B
Gressens, P
Nijboer, C
Year 2016
Journal name Progress in Neurobiology
Volume number 136
Start page 28
End page 49
Total pages 22
Publisher Pergamom Press
Abstract Preterm birth is an evolving challenge in neonatal health care. Despite declining mortality rates among extremely premature neonates, morbidity rates remain very high. Currently, perinatal diffuse white matter injury (WMI) is the most commonly observed type of brain injury in preterm infants and has become an important research area. Diffuse WMI is associated with impaired cognitive, sensory and psychological functioning and is increasingly being recognized as a risk factor for autism-spectrum disorders, ADHD, and other psychological disturbances. No treatment options are currently available for diffuse WMI and the underlying pathophysiological mechanisms are far from being completely understood. Preterm birth is associated with maternal inflammation, perinatal infections and disrupted oxygen supply which can affect the cerebral microenvironment by causing activation of microglia, astrogliosis, excitotoxicity, and oxidative stress. This intricate interplay of events negatively influences oligodendrocyte development, causing arrested oligodendrocyte maturation or oligodendrocyte cell death, which ultimately results in myelination failure in the developing white matter. This review discusses the current state in perinatal WMI research, ranging from a clinical perspective to basic molecular pathophysiology. The complex regulation of oligodendrocyte development in healthy and pathological conditions is described, with a specific focus on signaling cascades that may play a role in WMI. Furthermore, emerging concepts in the field of WMI and issues regarding currently available animal models are put forward. Novel insights into the molecular mechanisms underlying impeded oligodendrocyte maturation in diffuse WMI may aid the development of novel treatment options which are desperately needed to improve the quality-of-life of preterm neonates.
Subject Innate Immunity
Neurology and Neuromuscular Diseases
Keyword(s) Astrogliosis
Preterm birth
Therapeutic strategies
White matter injury
DOI - identifier 10.1016/j.pneurobio.2015.11.002
Copyright notice © 2015 Elsevier Ltd.
ISSN 0301-0082
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