Abstract
To date, miRNA expression studies on cerebral ischemia in both human and animal models have focused mainly on acute phase of ischemic stroke. In this study, we present the roles played by microRNAs in the spontaneous recovery phases in cerebral ischemia using rodent stroke models. Brain tissues were harvested at different reperfusion time points ranging from 0–168 hrs after middle cerebral artery occlusion using homologous emboli. MiRNA and mRNA expression profiles were investigated by microarray followed by multiple statistical analysis. Candidate transcripts were also validated by quantitative RT-PCR. Three specific groups of miRNAs were observed among a total of 346 differentially expressed miRNAs. miRNAs, miR-21, -142-3p, -142-5p, and -146a displayed significant upregulation during stroke recovery (48 hrs to 168 hrs) compared with those during acute phases (0 hrs to 24 hrs). On the other hand, an opposite trend was observed in the expression of miR-196a/b/c, -224 and -324-3p. Interestingly, miR-206, -290, -291a-5p and -30c-1*, positively correlated with the infarct sizes, with an initial increase up to 24hrs followed by a gradual decrease from 48 hrs to 168 hrs (R = 0.95). Taken together with the expression levels of corresponding mRNA targets, we have also found that Hedgehog, Notch, Wnt and TGF-β signaling pathways could play significant roles in stroke recovery and especially in neuronal repair.
Highlights
IntroductionThe possible strategies for ischemic stroke treatment include intravenous thrombolysis (rt-PA), neuroprotection and neuronal repair
Stroke is one of the leading causes of death and adult disability worldwide
We found miR-21 and miR-146a to be highly expressed in recovery phase compared to the acute phase of stroke and might be useful in predicting the recovery process (Figure 5, Table S1). miR-21 is known to prevent apoptosis by targeting Faslg [26]. miR-146a was reported to elicit neuroprotective effect by targeting Irak1 [27]
Summary
The possible strategies for ischemic stroke treatment include intravenous thrombolysis (rt-PA), neuroprotection and neuronal repair. Several studies on miRNA expression in stroke using human samples and animal models have been carried out [5,6,7,8]. These reports implicated the potential functions of miRNAs as biomarkers for diagnosis and prognosis as well as therapeutic targets in cerebral ischemia. This study was designed to identify temporal miRNA expression profiles from acute to recovery phase with more emphasis on the latter in order to understand the neuronal repair processes that follow cerebral ischemia
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