Timing-dependent neuroprotection of dexamethasone in neonatal hypoxic-ischemic brain injury mouse model : Transcriptomic insights into synaptic signaling and calcium homeostasis

Neuropathological analysis demonstrated that dexamethasone pretreatment attenuated brain injury. Differentially expressed genes (DEGs) were identified based on an adjusted p-value (FDR) < 0.05 using the Benjamini–Hochberg correction. A total of 962 DEGs were identified, including 407 upregulated and 555 downregulated genes.

Functional enrichment analysis revealed that upregulated genes were primarily associated with central nervous system development, synaptic signaling, and ionic homeostasis, whereas downregulated genes were mainly involved in cellular metabolic processes. Protein–protein interaction network analysis further demonstrated that DLG4, CALM1, and GRIN1 were highly interconnected within the enriched signaling pathways. Conclusion: Our findings demonstrate that dexamethasone provides time-dependent neuroprotection by stabilizing synaptic networks and modulating metabolic demand.

These results highlight the critical importance of early intervention and provide a molecular framework for developing pharmacological strategies against neonatal HI injury