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Orexin-A is a neuropeptide with potent neuroprotective activity towards cerebral ischemia-reperfusion (I/R) injury, but few studies have attempted to elucidate the mechanism. Herein, we performed global gene expression profiling of the hippocampus following reperfusion with Orexin-A using RNA sequencing (RNA-seq). RNA-seq identified 649 differentially expressed genes (DEGs) in the Orexin-A group compared with saline controls (I/R group), of which 149 were up-regulated and 500 were down-regulated. DEGs were confirmed using qRT-PCR, their molecular functions, biological processes and molecular components were explored using Gene Ontology (GO) analysis and 206 KEGG pathways were associated with Orexin-A treatment. MAPK, chemokine and calcium signalling pathways were mainly responsible for the neuroprotective effects of Orexin-A. Hspb1, Igf2 and Ptk2b were selected for functional interaction analysis by GeneMANIA. The results suggest that Orexin-A modifies gene expression in the hippocampus, leading to neuroprotection from I/R injury. The study provides a basis for future elucidation of the molecular mechanisms underlying Orexin-A.

RNA-seq expression profiling of rat MCAO model following reperfusion Orexin-A