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Vulnerability of premyelinating oligodendrocytes to white-matter damage in neonatal brain injury

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Abstract

Premature birth is a significant economic and public health burden, and its incidence is rising. Periventricular leukomalacia (PVL) is the predominant form of brain injury in premature infants and the leading cause of cerebral palsy. PVL is characterized by selective white-matter damage with prominent oligodendroglial injury. The maturation-dependent vulnerability of developing and premyelinating oligodendrocytes to excitotoxic, oxidative, and inflammatory forms of injury is a major factor in the pathogenesis of PVL. Recent studies using mouse models of PVL reveal that synapses between axons and developing oligodendrocytes are quickly and profoundly damaged in immature white matter. Axon-glia synapses are highly vulnerable to white-matter injury in the developing brain, and the loss of synapses between axons and premyelinating oligodendrocytes occurs before any cellular loss in the immature white matter. Microglial activation and astrogliosis play important roles in triggering white-matter injury. Impairment of white-matter development and function in the neonatal period contributes critically to functional and behavioral deficits. Preservation of the integrity of the white matter is likely key in the treatment of PVL and subsequent neurological consequences and disabilities.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Medicine, Institute for Pediatric Regenerative Medicine, School of Medicine, University of California at Davis, Sacramento, CA, 95817, USA

    Xiao-Bo Liu, Yan Shen, Jennifer M. Plane & Wenbin Deng

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  1. Xiao-Bo Liu
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  2. Yan Shen
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  3. Jennifer M. Plane
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  4. Wenbin Deng
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Correspondence to Wenbin Deng.

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Liu, XB., Shen, Y., Plane, J.M. et al. Vulnerability of premyelinating oligodendrocytes to white-matter damage in neonatal brain injury. Neurosci. Bull. 29, 229–238 (2013). https://doi.org/10.1007/s12264-013-1311-5

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  • DOI: https://doi.org/10.1007/s12264-013-1311-5

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