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Updated: Jun 3, 2026
Progenitor-derived Oligodendrocyte Culture System from Human Fetal Brain
Published on: December 20, 2012
The developing oligodendrocyte: key cellular target in brain injury in the premature infant
Joseph J Volpe1, Hannah C Kinney, Frances E Jensen
1Department of Neurology, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. joseph.volpe@childrens.harvard.edu
Insights
Premature infant brain injury targets developing oligodendrocytes. Understanding maturation-dependent vulnerability to hypoxia-ischemia and inflammation reveals therapeutic targets for neurodevelopmental disability.
Area of Science:
- Neuroscience
- Developmental Biology
- Neonatal Medicine
Background:
- Premature infant brain injury is a leading cause of neurodevelopmental disability.
- Cerebral white matter injury, particularly affecting developing oligodendrocytes, is a major concern.
- Premyelinated oligodendrocytes (pre-OLs) exhibit unique vulnerabilities during development.
Purpose of the Study:
- To review the cellular and molecular mechanisms underlying pre-OL vulnerability.
- To explore the role of hypoxia-ischemia and infection/inflammation in pre-OL injury.
- To identify potential therapeutic interventions for preventing brain injury in premature infants.
Main Methods:
- Analysis of human brain tissue and experimental models of neonatal brain injury.
- Investigation of maturation-dependent cellular and molecular events in oligodendrocytes.
- Identification of upstream (hypoxia-ischemia, infection/inflammation) and downstream (microglial activation, excitotoxicity, free radical attack) injury mechanisms.
Main Results:
- Premyelinated oligodendrocytes are uniquely vulnerable due to maturation-dependent factors.
- Hypoxia-ischemia and systemic infection/inflammation trigger injury through specific downstream pathways.
- Experimental models demonstrate that targeting these pathways offers significant protection.
Conclusions:
- Elucidation of pre-OL vulnerability provides a foundation for novel therapeutic strategies.
- Potential interventions targeting microglial activation, excitotoxicity, and free radical damage show promise.
- Clinical trials in premature infants are the crucial next step for validating these findings.
Abstract:
Brain injury in the premature infant, a problem of enormous importance, is associated with a high risk of neurodevelopmental disability. The major type of injury involves cerebral white matter and the principal cellular target is the developing oligodendrocyte. The specific phase of the oligodendroglial lineage affected has been defined from study of both human brain and experimental models. This premyelinating cell (pre-OL) is vulnerable because of a series of maturation-dependent events. The pathogenesis of pre-OL injury relates to operation of two upstream mechanisms, hypoxia-ischemia and systemic infection/inflammation, both of which are common occurrences in premature infants. The focus of this review and of our research over the past 15-20 years has been the cellular and molecular bases for the maturation-dependent vulnerability of the pre-OL to the action of the two upstream mechanisms. Three downstream mechanisms have been identified, i.e., microglial activation, excitotoxicity and free radical attack. The work in both experimental models and human brain has identified a remarkable confluence of maturation-dependent factors that render the pre-OL so exquisitely vulnerable to these downstream mechanisms. Most importantly, elucidation of these factors has led to delineation of a series of potential therapeutic interventions, which in experimental models show marked protective properties. The critical next step, i.e., clinical trials in the living infant, is now on the horizon.
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