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Neurobiology of injury to the developing brain

Nature Reviews Neurology volume 6, pages 328–336 (2010)Cite this article

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Abstract

Owing to improved survival rates of premature newborns, the number of very low birth weight infants is rising. Preterm infants display a greater propensity for brain injury caused by hypoxic or ischemic events, infection and/or inflammation that results in prominent white matter injury (WMI) than infants carried to full term. The intrinsic vulnerability of developing oligodendroglia to excitotoxic, oxidative and inflammatory forms of injury is a major factor in the pathogenesis of this condition. Furthermore, activated microglia and astrogliosis are critically involved in triggering WMI. Currently, no specific treatment is available for this kind of injury. Injury to the premature brain can substantially influence brain development and lead to disability. Impairment of the main motor pathways, such as the corticospinal tract, in the perinatal period contributes substantially to clinical outcome. Advanced neuroimaging techniques have led to greater understanding of the nature of both white and gray matter injury in preterm infants. Further research is warranted to examine the translational potential of preclinical therapeutic strategies for controlling such injury and preserving the integrity of motor pathways in preterm infants.

Key Points

  • Premature birth remains a substantial economic and public health burden

  • Periventricular leukomalacia is the predominant form of white matter injury (WMI) and the leading cause of cerebral palsy in premature infants

  • Maturation-dependent vulnerability of developing oligodendroglia to excitotoxicity and oxidative and inflammatory forms of injury is an important factor in the pathogenesis of WMI

  • Activated microglia and astrogliosis are critically involved in triggering WMI

  • Impairment of corticospinal tract development and function in the perinatal period contributes extensively to abnormalities of motor system function

  • Advanced neuroimaging techniques have led to greater understanding of the nature of white and gray matter injury in preterm infants

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Figure 1: Oligodendrocyte development.
Figure 2: Pathogenesis of cerebral white matter injury in the premature infant.

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Acknowledgements

The author thanks Dr. V. Selvaraj for his critical reading of this manuscript. This work was in part supported by grants from the NIH (RO1 NS059043 and RO1 ES015988), the National Multiple Sclerosis Society, the Roche Foundation for Anemia Research, the Feldstein Medical Foundation, and Shriners Hospitals for Children.

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  1. Department of Cell Biology and Human Anatomy, Institute for Pediatric Regenerative Medicine, School of Medicine, University of California Davis, 2425 Stockton Boulevard, Sacramento, 95817, CA, USA

    Wenbin Deng

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Deng, W. Neurobiology of injury to the developing brain. Nat Rev Neurol 6, 328–336 (2010). https://doi.org/10.1038/nrneurol.2010.53

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