Cited by 202Neonatal and fetal brain pathologyNeurogenesis and neuroplasticity mechanismsInfant Development and Preterm Care

Pathophysiology of glia in perinatal white matter injury

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Back, Stephen A., Rosenberg, Paul A.·2014·Glia

Abstract

Injury to the preterm brain has a particular predilection for cerebral white matter. White matter injury (WMI) is the most common cause of brain injury in preterm infants and a major cause of chronic neurological morbidity including cerebral palsy. Factors that predispose to WMI include cerebral oxygenation disturbances and maternal–fetal infection. During the acute phase of WMI, pronounced oxidative damage occurs that targets late oligodendrocyte progenitors (pre‐OLs). The developmental predilection for WMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible pre‐OLs that are vulnerable to a variety of chemical mediators including reactive oxygen species, glutamate, cytokines, and adenosine. During the chronic phase of WMI, the white matter displays abberant regeneration and repair responses. Early OL progenitors respond to WMI with a rapid robust proliferative response that results in a several fold regeneration of pre‐OLs that fail to terminally differentiate along their normal developmental time course. Pre‐OL maturation arrest appears to be related in part to inhibitory factors that derive from reactive astrocytes in chronic lesions. Recent high field magnetic resonance imaging (MRI) data support that three distinct forms of chronic WMI exist, each of which displays unique MRI and histopathological features. These findings suggest the possibility that therapies directed at myelin regeneration and repair could be initiated early after WMI and monitored over time. These new mechanisms of acute and chronic WMI provide access to a variety of new strategies to prevent or promote repair of WMI in premature infants. GLIA 2014;62:1790–1815

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  • The NMDAR is regulated by redox state: GRIN1 and GRIN2A possess pairs of redox-sensitive cysteine residues whose disulfide bond formation decreases NMDAR currents, while an overlapping group of cysteine residues are subject to inhibitory S-nitrosylation which facilitates disulfide bond formation.

    “The NMDAR is regulated by redox state: both GRIN1 and GRIN2A possess pairs of redox-sensitive cysteine residues whose disulfide bond formation decreases NMDAR currents 67,68 , while an overlapping group of cysteine residues are subject to inhibitory Snitrosylation which facilitates disulfide bond formation 67 .”

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  1. Brault S Martinez-Bermudez AK Roberts J 2nd Cui QL Fragoso G Hemdan S Liu HN Gobeil F Jr. Quiniou C Kermorvant-Duchemin E Cytotoxicity of the E(2)-isoprostane 15-E(2t)-IsoP on oligodendrocyte progenitors. Free Radic Biol Med 2004b 37 358 66 others 15223069
  2. Talos DM Follett PL Folkerth RD Fishman RE Trachtenberg FL Volpe JJ Jensen FE Developmental regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury. II. Human cerebral white matter and cortex. J Comp Neurol 2006b 497 61 77 16680761 PMC2987718
  3. Volpe JJ Neurology of the Newborn 2008a 399 407 W.B. Saunders Philadelphia

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Authors
Back, S. A., & Rosenberg, P. A.
Affiliations
  • Oregon Health & Science University (US)
  • Boston Children's Hospital (US)
Corresponding author
Back, Stephen A.
Venue
Glia
Publisher
Wiley
Published
2014-03-31
Volume
62
Issue
11
Pages
1790-1815
ISSN
  • 0894-1491 (ISSN-L)
  • 1098-1136
OpenAlex
W1494362497
Cited by
202
References
345
Citations by year
2026: 14 · 2025: 12 · 2024: 13 · 2023: 4 · 2022: 16 · 2021: 8 · 2020: 11 · 2019: 22 · 2018: 19 · 2017: 37 · 2016: 19 · 2015: 18 · 2014: 8
FWCI
4.12
Type
journal article
Language
en
Open access
Locations
  • Glia (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Neurological Diseases and Stroke (NIH) (1R01NS054044 and R37NS045737)
  • National Institute of Aging (NIH) (1R01AG031892-01)
  • American Heart Association (11GRNT7510072)
  • March of Dimes Birth Defects Foundation (# 6-FY11-323)
  • NIH (P30 HD018655 and R01 NS066019, Whitehall Foundation and Baby Alex Foundation.)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
Keywords
preterm brain injury, oligodendrocyte progenitors, oxidative stress, reactive oxygen species, glutamate excitotoxicity, cytokines, adenosine, reactive astrocytes, remyelination, white matter repair, cerebral palsy, cerebral hypoxia, maternal-fetal infection
MeSH terms
Animals, Humans, Myelin Sheath, Neuroglia, Receptors, Glutamate, Oxidative Stress, Premature Birth, Leukoencephalopathies

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