Gene. 2025 Mar 8:149363. doi: 10.1016/j.gene.2025.149363. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVE: Neonatal hypoxic-ischemic encephalopathy (HIE) remains a critical challenge in perinatal medicine. This study aimed to elucidate the transcriptomic landscape, focusing on long non-coding RNAs (lncRNAs) expression patterns in the brain tissues of a neonatal rat model of HIE.
METHODOLOGY: We employed a modified Rice-Vannucci model to induce HIE in postnatal day 4 (P4) rats. The experimental groups were subjected to either 5 or 7 min of hypoxia (0 % O2, 100 % N2), while control animals were exposed to normoxic conditions.
RESULTS: RNA sequencing revealed a complex transcriptomic landscape in HIE brains, with approximately 80 million differentially expressed lncRNAs compared to controls. ELISA results demonstrated a significant upregulation of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and a concomitant decrease in anti-inflammatory IL-10 levels in brain tissue of HIE rats. qRT-PCR analysis revealed aberrant expression of several miRNAs. Biochemical assays indicated a marked reduction in superoxide dismutase (SOD) activity and an increase in malondialdehyde (MDA) content in HIE brain tissues.
CONCLUSIONS: This study highlights the potential regulatory roles of lncRNAs in HIE brains. The intricate interplay between lncRNAs, miRNAs, and mRNAs and alterations in inflammatory and oxidative stress markers suggests a complex regulatory network governing HIE pathogenesis.
PMID:40064305 | DOI:10.1016/j.gene.2025.149363
