Highlights
- Intermittent hypoxia induces multiphasic vascular changes in the developing cerebellum, with initial expansion at P4 followed by normalization and persistent long-term alterations.
- Novel 3D imaging workflow combining IMARIS and VesselVio enables quantitative analysis of superficial versus deep cerebellar vascular networks.
- Transcriptomic dysregulation of 23 angiogenesis genes persists long after cessation of hypoxic exposure, particularly affecting VEGF, angiopoietin, and MMP pathways.
- Superficial and deep vascular networks respond differently to intermittent hypoxia, revealing distinct remodeling patterns throughout development.
- Vascular disruptions parallel neurogenic deficits, highlighting the interconnected nature of angio- and neurogenesis in apnea of prematurity.
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Citation
BibTeX citation:
@article{rodriguez-duboc2026,
author = {Rodriguez-Duboc, Agalic and Racine, Camille and
Basille-Dugay, Magali and Vaudry, David and Gonzalez, Benjamin and
Burel, Delphine},
title = {Innovative {3D-image} Analysis of Cerebellar Vascularization
Highlights Angiogenic Gene Dysregulations in a Murine Model of Apnea
of Prematurity},
journal = {The Cerebellum},
volume = {25},
number = {3},
pages = {62},
date = {2026-04-28},
url = {https://link.springer.com/article/10.1007/s12311-026-02006-1},
doi = {10.1007/s12311-026-02006-1},
issn = {1473-4222},
langid = {en},
abstract = {Apnea of prematurity (AOP) affects 50\% of preterm infants
causing intermittent hypoxia (IH), which can lead to long-term
neurodevelopmental deficits. Cerebellar abnormalities have been
observed in AOP but the relationship between vascular alterations
and neural development remains unclear. This study investigates how
IH affects cerebellar angiogenesis using a murine model of AOP. We
developed an innovative 3D imaging workflow combining IMARIS and
VesselVio software to quantitatively analyze cerebellar
vascularization at different postnatal stages (P4, P8, P12, P21, and
P70). We correlate these results with a transcriptomic analysis of
23 angiogenesis-related genes in the same stages to uncover the
associated molecular pathways. We found that IH induced significant
vascular changes, particularly at P4, with a global increase in
vascular-network dimensions. By P8, the vascular network normalized,
but genes were downregulated in all pathways studied. After P12, at
the end of the IH protocol, transcriptional regulations vary but
persist long-term. Moreover, differential analysis showed distinct
effects on superficial versus deep vascular networks, allowing for a
more precise understanding of remodeling patterns throughout
development. Overall, transcriptomic changes were associated with
morphological alterations in a time-dependent manner, suggesting a
multiphasic IH response through development with lasting effects.
Key regulations included VEGF, angiopoietin, and matrix
metalloprotease signaling. These findings demonstrate that IH
disrupts cerebellar angiogenesis in parallel with neurogenesis,
potentially contributing to the neurodevelopmental deficits observed
in AOP. Thus, the interconnected nature of angio- and neurogenesis
during cerebellar development makes it crucial to take vascular
aspects into account in therapeutic approaches to neurodevelopmental
disorders.}
}
For attribution, please cite this work as:
Rodriguez-Duboc, A., Racine, C., Basille-Dugay, M., Vaudry, D.,
Gonzalez, B., & Burel, D. (2026). Innovative 3D-image analysis of
cerebellar vascularization highlights angiogenic gene dysregulations in
a murine model of apnea of prematurity. The Cerebellum,
25(3), 62. https://doi.org/10.1007/s12311-026-02006-1