Early transcriptional responses reveal cell type-specific vulnerability and neuroprotective mechanisms in the neonatal ischemic hippocampus.

ABSTRACT: Neonatal hypoxic-ischemic (H-I) brain injury, a leading cause of neurodevelopmental disabilities, severely affects the metabolically active and neurogenic hippocampus. To investigate its acute effects and identify drug targets for early therapeutic windows, we applied single-nucleus RNA sequencing on postnatal day 8 (P8) mouse hippocampi under sham, hypoxic, and hypoxic-ischemic conditions. We constructed a comprehensive hippocampal cell atlas and developed a machine-learning classifier for precise cell type identification. Our analysis reveals early vulnerabilities in mature neurons and notable resilience in immature DG, GABAergic, and Cajal-Retzius cells following H-I. Gene regulatory network analysis identified key transcription factors associated with neuronal vulnerability, along with

SUBMITTER: Ianevski A 

PROVIDER: S-EPMC12228329 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature