Cerebral Whole Transcriptome Differences Between Thrombus Embolic Stroke And Cholesterol Embolic Stroke Rat Models

BackgroundCholesterol embolic stroke and thrombus embolic stroke are the two most common types of ischemic stroke.Although there are obvious differences in embolic components,clinical manifestations and treatment between the two types of ischemic stroke,the pathological mechanism leading to the difference between the two types of stroke remains unclear.The effect of cholesterol crystals on ischemic stroke is also less concerned.The purpose of this study was to compare the differences between cholesterol embolic stroke and thrombus embolic stroke in rat models,and to explore the underlying pathological mechanism of the differences through transcriptome sequencing,so as to provide new ideas for the clinical prevention and treatment of the two ischemic stroke.ObjectiveTo construct cholesterol embolic stroke model and thrombus embolic stroke model in rats and compare the difference of infarct volume,neurobehavioral deficits and blood-brain-barrier damage,then predict the potential mechanism that leading to the different manifestation between the two stroke model by RNA sequencing.MethodsIn this study,the rat models of cholesterol embolic stroke(by injecting cholesterol emboli)and thrombus embolic stroke(by injecting thrombus emboli)were constructed by the microembolization method.Longa score was used to evaluate neurological deficits,TTC staining was used to detect infarct volume,Evans blue staining was used to detect the degree of blood-brain barrier damage.We further used high-throughput RNA sequencing to identify differentially expressed RNA(including mRNA,long non-coding RNA,microRNA and circular RNA)in brain tissue of the two models,GO and KEGG analysis were used to predict the function of differentially expressed RNA,Pearson correlation coefficient and MiRanda database were used to predict competitive endogenous RNA(ceRNA)pairs.ResultsThe rats model results showed that neurological deficit,infarct volume and blood-brain-barrier damage degree in cholesterol group was lighter than thrombotic group,for RNA-seq,1563 mRNAs,705 lncRNAs,149 circRNAs,29 miRNAs were differentially expressed and 552 ceRNAs of lncRNA-miRNA-mRNA pairs and 421 ceRNAs of circRNA-miRNA-mRNA pairs were predicted.GO and KEGG pathways predict the potential function of differentially expressed RNA.Some differentially expressed RNAs are widely involved in inflammation,cell survival and lipid metabolism related pathways,including MAPK,TNF,IL-17,PI3 K,PPAR pathway and L-methionine synthesis process.ConclusionThese results indicated that brain injury in the cholesterol embolic stroke group was lighter than that in the thrombus embolic stroke group.RNA high-throughput sequencing analyzed the differentially expressed RNAs in the two groups and predicted their potential function.Some of these RNA,lncRNA and circRNA may be involved in the pathways of inflammation,cell survival and lipid metabolism,suggesting that these differentially expressed RNA may play a role through these pathways and affect the prognosis of the two embolic stroke rat models.However,further experiments are needed to explore the mechanism of Scd and other differentially expressed RNAs involved in the pathogenesis of cholesterol embolic stroke and thrombus embolic stroke,so as to provide theoretical basis for clinical diagnosis and treatment.