Faculty, Staff and Student Publications
Language
English
Publication Date
11-28-2025
Journal
Journal of Neuroinflammation
DOI
10.1186/s12974-025-03599-w
PMID
41316264
PMCID
PMC12870941
PubMedCentral® Posted Date
11-28-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Neonatal intraventricular hemorrhage (IVH) is a major complication of preterm birth, yet how developmental stage influences the brain's response to injury remains unclear. We performed single-nucleus RNA sequencing on rat brains 24 h after IVH at postnatal day 2 (PND2) or day 5 (PND5) to define transcriptional responses across cell types. We identified 42 distinct cell populations and found that PND5 brains exhibited a markedly stronger immune and inflammatory response to IVH, with a threefold increase in differentially expressed genes compared to PND2. Microglia were the most perturbed cell type at both stages, showing increased oxidative stress and polarization toward both pro- and anti-inflammatory phenotypes at PND5. Ligand-receptor and regulon analysis revealed a shift from reparative IGF2 and TGF-β signaling at PND2 to proinflammatory Wnt signaling and activation of Runx1 and Stat5 at PND5. These findings highlight the importance of developmental timing in shaping the neuroimmune response to IVH and identify potential stage-specific therapeutic targets.
Keywords
Animals, Rats, Animals, Newborn, Transcriptome, Rats, Sprague-Dawley, Cerebral Intraventricular Hemorrhage, Male, Female, Brain, Gene Expression Regulation, Developmental, Microglia
Published Open-Access
yes
Recommended Citation
Wallace-Anthony, Elizabeth; Zamorano, Miriam; Vekaria, Hemendra J; et al., "Developmental Stage-Dependent Transcriptomic Responses to Neonatal Intraventricular Hemorrhage" (2025). Faculty, Staff and Student Publications. 6358.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6358
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