Bioinformatics analysis of microRNA expression profiles in rat cortex following focal cerebral ischemia and reperfusion

Introduction Ischemic stroke, a serious disease of brain, is usually derived from the obstruction of blood supply artery. As one of the leading cause of death and disability worldwide, it brings about heavy medical burden. The main therapeutic methods was making recanalization to restore blood flow and obtain reperfusion [1].But reperfusion itself could cause additional and unexpected brain damage termed as cerebral ischemia/ reperfusion (CIR) injury[2], which resulted in secondary energy failure and ensuing cell death in a delayed manner. There are some evidences supported this pathological process from animal model studies of gerbil[3] and rats[4], even from human patients trails[5]. And the pathophysiological mechanisms of CIR injury was very complex, including intracellular calcium overload, calcium sensitive proteinase activated, excitatory amino acid release, reactive oxygen species excessive generated, lipid peroxidation[6], inflammation, and mitochondrial respiratory function reduced[7]. , etc. And microRNA (miRNA) has been reported to implicate with the pathophysiological mechanisms of CIR injury[8] [9].However, little was known about the bioinformatics of miRNAs genomics played in the molecular machenisms of CIR injury, and how they performed their effects. MicroRNAs (miRNAs) are small noncoding single-stranded RNA molecules with mature transcripts of 18 to 25 nucleotides long that act as negative regulators of gene expression, which binds to the 3’-untranslated region (UTR) of complementary or partially complementary target messenger RNAs (mRNAs) and thereby downregulates the target mRNA via degradation or translational inhibition[10]. In CNS, miRNAs have been correlated with modulation of multiple diseases and pathological processes, such as neurodegenerative disorders[11], cancers[12], stroke[13] , and cerebral ischemia reperfusion injury[14]. And the miRNA expressing profiles in CIR animal models are increasingly reported[15] [16] [17][18]. However, these studies merely provided the superficial changes of these miRNAs[19] [20] or focus on the role of single miRNA in cerebral ischemia[21][22], lacking of comprehensive analysis for their biological functions and downstream signaling transduction pathways. Abstract Ischemic stroke is a serious disease of brain caused by the blood obstruction. Reperfusion is a necessary treatment for ischemic stroke, but itself also causes the secondary injury termed cerebral ischemia/ reperfusion (CIR) injury. In order to elucidate the molecular mechanism of CIR injury, We detected the miRNAs expression profile in rats cortex after focal cerebral ischemia and reperfusion by using miRNA microarray technique, and systematically analyzed the gene ontology function classifications as well as signaling pathways of genes targeted by these differentially expressing miRNAs with bioinformatics tools. The results showed that miRNAs expression profiles were significantly changed in the reperfusion phrase of focal cerebral ischemia, and a total of 15 miRNAs were up-regulated and 44 miRNAs down-regulated. The target genes of these differentially expressed miRNAs were mainly involved in metabolic process and cellular process, which were identified as the hub node of miRNA-GO-network. The most correlated pathways included D-Glutamine and D-glutamate metabolism, renin-angiotensin system, peroxisome, PPAR signaling pathway, SNARE interactions in vesicular transport, and calcium signaling pathway. Our study suggested that miRNAs might play an important role in the pathological process of cerebral ischemia/ reperfusion injury. Understanding miRNAs expression and functions may shed a new light on illustrating the molecular mechanism of CIR injury.