Inflammatory reprogramming of immature oligodendrocytes perturbs myelination and neurodevelopment in a dual-hit model of preterm brain injury

Brain, Behavior, & Immunity - Health · Published 2026-05-14 · DOI 10.1016/j.bbih.2026.101253

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Authors (4)

Xueling Ma, Wen Jia, Xingdao Zhang, Yuan Shi

Abstract

Background: Preterm infants are highly susceptible to white matter injury, in part due to exposure to perinatal inflammation and/or hypoxia. These insults disrupt oligodendrocyte (OL) lineage maturation, leading to impaired myelination and neurodevelopmental deficits; however, the underlying mechanisms remain incompletely understood. Methods: A dual-hit rat model was established to recapitulate key features of preterm brain injury. Myelination, behavior, and brain function and structure were assessed. The early developmental trajectory of immature OLs was tracked, and the cells were isolated for transcriptomic profiling. Results: The dual-hit model exhibited delayed myelination, accompanied by long-term behavioral abnormalities, reduced hippocampal functional connectivity, and decreased hippocampal gray matter volume. A marked surge in immature OL death was observed around postnatal day 9. Transcriptomic profiling at this developmentally vulnerable time point revealed pronounced inflammatory reprogramming within immature OLs. Conclusions: Perinatal inflammation combined with postnatal hypoxia delays myelination and leads to persistent behavioral and brain structural and functional alterations, with immature OLs loss and inflammatory reprogramming emerging as potential drivers of preterm brain injury.

Abstract from DOAJ. Public domain (CC0 1.0).

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Publication details

Year
2026

Citation

Ma, X., Jia, W., Zhang, X., et al. (2026). Inflammatory reprogramming of immature oligodendrocytes perturbs myelination and neurodevelopment in a dual-hit model of preterm brain injury. Brain, Behavior, & Immunity - Health. https://doi.org/10.1016/j.bbih.2026.101253

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