Identification Of Differentially Expressed Genes And Their Functions In Hypoxic-ischemic Encephalopathy By Bioinformatics Analysis

[Background]Neonatal hypoxic-ischemic encephalopathy refers to the brain hypoxic-ischemic damage caused by perinatal asphyxia,which can leave different degrees of nervous system sequelae.After the incubation period,there will be secondary energy failure,which is characterized by excitotoxic injury,oxidative stress disorder,inflammatory cascade and mitochondrial energy failure.There is a treatment window before the secondary deterioration period.Starting mild hypothermia within 6 hours after injury is an effective brain protective measure confirmed by current studies,which can reduce the degree of energy failure and reduce neuronal injury.The diagnosis of neonatal HIE is mainly based on clinical manifestations,imaging and neuroelectrophysiological examination.These tests take some time to determine whether the newborn has brain injury,so some children with brain injury miss the best treatment time.Therefore,the identification of specific biochemical markers of intracranial tissue pathological injury is of great significance for disease judgment,prognosis evaluation and early intervention.[Research purpose]Explore the differentially expression genes and functional enrichment at different time points after neonatal hypoxic-ischemic(HI)brain injury,and explore potential biomarkers related to HIE by screening key genes.[Materials and methods]The GSE23317 dataset were acquired from the GEO database.We use GEO2 R to screen DEGs.GO and KEGG pathway analyses were performed using DAVID database.PPI network of the DEGs were drawn to show the functional interactions using the STRING online database.The top 10 key genes in PPI network were extracted using the MCC method of the Cytoscape plug-in cyto Hubba.[Results]A total of 165 DEGs were predicted at 3 hours after injury,and were mainly enriched in neutrophil chemotaxis,cell cycle,stress,TNF signaling pathway,Toll-like receptor signaling pathway.The key genes were related to the immediate early reaction,inflammation and immune response.A total of 58 DEGs were identified at8 h and 24 h after injury.These genes were enriched in granulocytic chemotaxis,cell response to interferon-γ,cell to interleukin-1,cytokine receptor interaction,chemokine signaling pathway,and Toll-like receptor signaling pathway.The key genes were related to inflammation,innate immune response and chemotaxis.[Conclusion]1.Among the 10 key genes at 3 hours after injury,FOS,JUN,JUNB and EGR1 were immediate early response genes,and DUSP1,SOCS3,CEBPB,NFKBIA,NFk BIZ,ATF3 genes were associated with inflammation and immune response.2.The key genes TIMP1,AGT,C1 QB,SOCS3,CCL3,CCL4,CD14,CXCL1,ARG1 and LCN2 at 8 hours and 24 hours after injury were related to inflammatory reaction,innate immune reaction and chemotaxis.3.Compared with the late stage of injury,the expression changes of immediate early response genes appear in the early stage of injury,which provides a new way of thinking about the biological markers of HIE.4.Inflammatory response,innate immune response and chemotaxis are involved in the occurrence and development of HIE,speculating that the immune response after brain injury may become a potential candidate for neuroprotection strategies5.The results of this study will help us to understand the potential genes and functional pathways in the development of HIE,but further molecular experiments are still needed to confirm the candidate genes and related pathways selected in our study.