Bioinformatic Analysis of Differentially Expressed Genes Involved in the Post-hypoxic Ischemic Brain Damage of Newborn Rats

Objective To analyze the differentially expressed genes (DEGs) in cerebral cortices of rats which were seven weeks after neonatal hypoxic ischemic brain damage (HIBD) and elucidate the biological significance of the DEGs. Methods The gene expression profile of GSE37777, including 4 HI samples subjected to HIBD and 4 normal controls, was downloaded from the Gene Expression Omnibus database (GEO). DEGs were screened using the R package in HIBD groups compared with normal controls. Pathway enrichment analysis was carried out using the Cytoscape plug-in ClueGO+Cluepedia and a functionally grouped pathway network of DEGs was constructed and analyzed. Besides, the protein-protein interaction (PPI) network was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape. Results A total of 973 DEGs were identified in HIBD group compared with the control group, including 599 up-regulated and 374 down-regulated genes. Furthermore, a functionally grouped pathway network of DEGs was constructed and hedgehog signaling pathway were identified. Shh and Dhh which were Hedgehog signaling pathway-related genes and the Wnt signaling pathway-related genes Wnt1, Wnt2B, and Wnt5 were up-regulated in HIBD group. Furthermore, Ccnd1, Shh, Ret and Gli3 were hub proteins in the PPI network and up-regulated Shh and Dhh, down-regulated Ccnd1 and Gli3 were noticed. Conclusion Our results showed that Hedgehog and Wnt signaling pathway may be activated HIBD group. Additionally, Shh and Ret which were related to the repair process of brain damage were up-regulated. Continuous repair process may exist in the cerebral cortices of rats which were seven weeks after neonatal HIBD.