Global gene expression profile of cerebral ischemia-reperfusion injury in rat MCAO model

Abstract

It is well-established that reperfusion following cerebral ischemic injury gives rise to secondary injury accompanied by structural and functional damage. However, it remains unclear how global genes changes in cerebral ischemia-reperfusion injury (IRI). This study investigated global gene expression in the hippocampi of Wistar rats following transient cerebral IRI using an RNA-sequencing strategy. The results revealed ≥2-fold up-regulation of 156 genes and ≥2-fold down-regulation of 26 genes at 24 h post-reperfusion. Fifteen differentially expressed genes were selected to confirm the RNA-sequencing results. Gene expression levels were dynamic, with the peak expression level of each gene occurring at different time points post-reperfusion. Gene Ontology (GO) analysis classified the differentially expressed genes as mainly involved in inflammation, stress and immune response, glucose metabolism, proapoptosis, antiapoptosis, and biological processes. KEGG pathway analysis suggested that IRI activated different signaling pathways, including focal adhesion, regulation of actin cytoskeleton, cytokine-cytokine receptor interaction, MAPK signaling, and Jak-STAT signaling. This study describes global gene expression profiles in the hippocampi of Wistar rats using the middle cerebral artery occlusion (MCAO) model. These findings provide new insights into the molecular pathogenesis of IRI and potential drug targets for the prevention and treatment of IRI in the future.

Astragaloside IV Protects Rat Cardiomyocytes from Hypoxia-Induced Injury by Down-Regulation of miR-23a and miR-92a

“…In the setting of ischaemia-reperfusion injury, several kinases signaling have been implicated through their effects on cell death and survival, including PI3K/AKT, MAPK/ERK, and JAK/STAT [35,36]. It has been demonstrated in the myocardium that the activation of PI3K/AKT and MAPK/ERK pathways by procedures such as ischaemic pre-or postconditioning or by the administration of pharmacological agents is crucial for the salvage of the ischaemic/reperfused myocardium [37][38][39].…”

The Role of Noncoding RNAs in Brain Cells during Rat Cerebral Ischemia

“…These investigators detected 182 differentially expressed genes (DEGs), most of which were upregulated [17]. A Gene Ontology analysis showed that these DEGs were mainly associated with inflammation, stress, immune response, glucose metabolism, and apoptosis [17]. Our analysis of gene expression under tMCAO conditions using RNA-Seq confirmed these results.…”

“…An increase of the mRNA level of the gene for INOS, encoding an enzyme for the synthesis of NO, also participating in the development of the inflammatory response in the lesion, was also noted [22,25]. In the ischemia-reperfusion model, it was also shown that cytokines (IL-1β, IL6), adhesion molecules (ICAM1, E-selectin, MMP-9), MAPK kinase, and c-fos transcription factors were involved in the development of inflammation [17,20,23,[26][27][28][29]. Wang et al studied the molecular mechanism of ischemia-reperfusion pathogenesis using genome-wide transcriptome analysis (RNA-Seq) in the hippocampus of rats at 24 h after tMCAO.…”

“…The most frequently used tMCAO model showed a reorganization of the functioning of many genes in various areas of rodent brains, including the infarction center, during the first day after the transient occlusion [15,[17][18][19]. In particular, activation of the transcription factor Nf-κb was shown.…”

“…Wang et al studied the molecular mechanism of ischemia-reperfusion pathogenesis using genome-wide transcriptome analysis (RNA-Seq) in the hippocampus of rats at 24 h after tMCAO. These investigators detected 182 differentially expressed genes (DEGs), most of which were upregulated [17]. A Gene Ontology analysis showed that these DEGs were mainly associated with inflammation, stress, immune response, glucose metabolism, and apoptosis [17].…”