Dataset Information

Cryptotanshinone Attenuates Oxygen-Glucose Deprivation/ Recovery-Induced Injury in an in vitro Model of Neurovascular Unit.

ABSTRACT: Cryptotanshinone (CTs), an active component isolated from the root of Salvia miltiorrhiza (SM), has been shown to exert potent neuroprotective property. We here established an oxygen-glucose deprivation/recovery (OGD/R)-injured Neurovascular Unit (NVU) model in vitro to observe the neuroprotective effects of CTs on cerebral ischemia/reperfusion injury (CIRI), and explore the underlying mechanisms. CTs was observed to significantly inhibit the OGD/R-induced neuronal apoptosis, and decease the activation of Caspase-3 and the degradation of poly-ADP-ribose polymerase (PARP), as well as the increase of Bax/Bcl-2 ratio in neurons under OGD/R condition. The inhibitory effects of CTs on neuron apoptosis were associated with the blocking of mitogen-activated protein kinase (MAPK) signaling pathway. CTs also remarkably ameliorated OGD/R-induced reduction of transepithelial electrical resistance (TEER) values and the increase of transendothelial permeability coefficient (Pe) of sodium fluorescein (SF) by upregulating the expression of ZO-1, Claudin-5, and Occludin in brain microvascular endothelial cells (BMECs), which might be related to the down-regulation of matrix metalloproteinase (MMP)-9 expression. Based on these findings, CTs may play a neuroprotective role in OGD/R injure in NVU models in vitro by inhibiting cell apoptosis and alleviating the damage of blood-brain barrier (BBB).

SUBMITTER: Zhao H

PROVIDER: S-EPMC6482155 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Cryptotanshinone Attenuates Oxygen-Glucose Deprivation/ Recovery-Induced Injury in an <i>in vitro</i> Model of Neurovascular Unit.

Zhao Hongye H Zheng Tiezheng T Yang Xiaohan X Fan Ming M Zhu Lingling L Liu Shuhong S Wu Liying L Sun Changkai C

Frontiers in neurology 20190418

Cryptotanshinone (CTs), an active component isolated from the root of Salvia miltiorrhiza (SM), has been shown to exert potent neuroprotective property. We here established an oxygen-glucose deprivation/recovery (OGD/R)-injured Neurovascular Unit (NVU) model <i>in vitro</i> to observe the neuroprotective effects of CTs on cerebral ischemia/reperfusion injury (CIRI), and explore the underlying mechanisms. CTs was observed to significantly inhibit the OGD/R-induced neuronal apoptosis, and decease ...[more]

PMID: 31057477

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Project description:Circular RNAs (circRNAs) are generated by head-to-tail splicing and are ubiquitously expressed in all multicellular organisms. Their important biological functions are increasingly recognized. Cerebral ischemia reperfusion injury-induced brain microvascular endothelial cell dysfunction is an initial stage of blood-brain barrier disruption. The expression profile and potential function of circRNAs in brain microvascular endothelial cells is unknown. Rat brain microvascular endothelial cells were extracted and cultured in glucose-free medium for 4 hours with 5% CO2 and 95% N2, and the medium was then replaced with complete growth medium for 6 hours. The RNA in these cells was then extracted. The circRNA was identified by Find_circ and CIRI2 software. Functional and pathway enrichment analysis of genes that were common to differentially expressed mRNAs and circRNA host genes was performed by the Database for Annotation, Visualization and Integrated Discovery Functional Annotation Tool. Miranda software was used to predict microRNAs that were potentially spong-ed by circRNAs. Furthermore, cytoscape depicted the circR-NA-microRNA interaction network. The results showed that there were 1288 circRNAs in normal and oxygen-glucose deprived/recovered primary brain microvascular endothelial cells. There are 211 upregulated and 326 downregulated differentially expressed circRNAs. The host genes of these differentially expressed circRNAs overlapped with those of differentially expressed mRNAs. The shared genes were further studied by functional enrichment analyses, which revealed that circRNAs may contribute to calcium ion function and the cyclic guanosine 3',5'-monophosphate (CAMP) dependent protein kinase (PKα) signaling pathway. Next, quantitative reverse transcription polymerase chain reaction assays were performed to detect circRNA levels transcribed from the overlapping host genes. Eight out of the ten circRNAs with the highest fold-change identified by sequencing were successfully verified. Subsequently, the circRNA-microRNA interaction networks of these eight circRNAs were explored by bioinformatic analysis. These results demonstrate that altered circRNAs may be important in the pathogenesis of cerebral ischemia reperfusion injury and consequently may also be potential therapeutic targets for cerebral ischemia diseases. All animal experiments were approved by the Chongqing Medical University Committee on Animal Research, China (approval No. CQMU20180086) on March 22, 2018.

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Dataset Information

Cryptotanshinone Attenuates Oxygen-Glucose Deprivation/ Recovery-Induced Injury in an in vitro Model of Neurovascular Unit.

Publications

Cryptotanshinone Attenuates Oxygen-Glucose Deprivation/ Recovery-Induced Injury in an <i>in vitro</i> Model of Neurovascular Unit.

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