Systematic Analysis of RNA Expression Profiles in Different Ischemic Cortices in MCAO Mice

The prognosis of ischemic stroke patients is highly associated with the collateral circulation. And the competing endogenous RNAs (ceRNAs) generated from different compensatory supply regions may also involve in the regulation of ischemic tissues prognosis. In this study, we found the apoptosis progress of ischemic neurons in posterior circulation-supplied regions (close to PCA, cortex2) was much slower than that in anterior circulation-supplied territory (close to ACA, cortex1) in MCAO-3-h mice. Using the RNA sequencing and functional enrichment analysis, we analyzed the difference between RNA expression profile in cortex1 and cortex2 and the related biological processes. The results indicated that the differential expressed ceRNAs in cortex1 were involved in cell process under acute injury, while the differential expressed ceRNAs in cortex2 was more likely to participate in long-term injury and repair process. Besides, by establishing the miRNA-ceRNA interaction network we further sorted out two specifically distributed miRNAs, namely mmu-miR446i-3p (in cortex1) and mmu-miR3473d (in cortex2). And the specifically increased mmu-miR3473d in cortex2 mainly involved the angiogenesis and cell proliferation after ischemic stroke, which may be the critical reason for the longer therapeutic time window in cortex2. In conclusion, the present study reported the specific changes of ceRNAs in distinct compensatory regions potentially involved in the evolution of cerebral ischemic tissues and the unbalance prognosis after stroke. It provided more evidence for the collateral compensatory effects on patients' prognosis and carried out the new targets for the ischemic stroke therapy.

Automated summary

The prognosis of ischemic stroke patients is closely associated with collateral circulation. Competing endogenous RNAs (ceRNAs) generated from different compensatory supply regions may also play a role in regulating the prognosis of ischemic tissues. This study analyzed the RNA expression profiles and biological processes in two distinct compensatory regions in mice with middle cerebral artery occlusion (MCAO) and identified specific changes in ceRNAs that are potentially involved in the evolution of cerebral ischemic tissues and the unbalanced prognosis after stroke. Furthermore, specific miRNAs, mmu-miR446i-3p and mmu-miR3473d, were found to be involved in angiogenesis and cell proliferation after ischemic stroke. These findings provide evidence for the collateral compensatory effects on patients' prognosis and identify new targets for ischemic stroke therapy.