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Brain Res Bull ; 185: 39-48, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35452749


Remote ischemic postconditioning (RIPostC) is a protective procedure for brain damage caused by ischemia/reperfusion (IR), yet the mechanism of this treatment remains to be elucidated. Circular RNAs (circRNAs) are endogenous non-coding RNAs that have recently been recognized to play vital roles in ischemic brain injury. The aim of this study was to explore the role of circRNAs in the protective mechanism of RIPostC and to analyze the circRNA-microRNA (miRNA) regulation network in RIPostC. Nine rats were assigned randomly into three groups (three rats per group): sham, IR, and RIPostC. Their brain tissues were extracted for next-generation RNA sequencing and bioinformatics analysis was performed for two comparisons: sham vs. IR and IR vs. RIPostC. The expression patterns of selected circRNAs and miRNAs were validated by quantitative real-time PCR (qPCR). We detected 82 upregulated and 51 downregulated circRNAs and 137 upregulated and 127 downregulated miRNAs in the IR group compared with the sham group, and 41 upregulated and 100 downregulated circRNAs and 45 upregulated and 64 downregulated miRNAs in the RIPostC group compared with the IR group. The proposed competitive endogenous RNA (ceRNA) network, which included 24 circRNAs, 20 miRNAs, and 145 mRNAs, indicated that the dysregulated circRNAs played important roles in brain IR injury. On the basis of the expression patterns of selected circRNAs, miRNAs, and mRNAs obtained by qPCR, we proposed a circRNA_0002286-miR-124-3p-VLCAD pathway. In PC12 cell, the expression level of miR-124-3p was significantly upregulated when the expression of circRNA_0002286 was repressed and the expression level of VLCAD (very-long chain acyl-CoA dehydrogenase) was significantly downregulated, which suggested that circRNA_0002286 may act as a miRNA sponge for miR-124-3p to regulate the expression of VLCAD. We found that upregulation of circRNA_0002286 attenuated IR injury and was associated with downregulation of miR-124-3p and upregulation of VLCAD. This is the first time that circRNAs have been shown to be closely related to brain IR injury and RIPostC and suggests that targeting the circRNA_0002286-miR-124-3p-VLCAD pathway might attenuate brain IR injury.

Neural Regen Res ; 17(6): 1299-1309, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34782575


During acute reperfusion, the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes. However, whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear. In this study, RNA isolation and library preparation was performed for long noncoding RNA sequencing, followed by determining the coding potential of identified long noncoding RNAs and target gene prediction. Differential expression analysis, long noncoding RNA functional enrichment analysis, and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats. Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery. Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke. The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke. The predicted target genes of some of the identified long noncoding RNAs (cis targets) were related to the cellular response to ischemia and stress, cytokine signal transduction, inflammation, and apoptosis signal transduction pathways. In addition, 15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning. Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis. Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction. These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke. The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University (approval No. KMMU2018018) in January 2018.

Metab Brain Dis ; 36(1): 53-65, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33044640


Ischemic postconditioning (PostC) conventionally refers to a series of brief blood vessel occlusions and reperfusions, which can induce an endogenous neuroprotective effect and reduce cerebral ischemia/reperfusion (I/R) injury. Depending on the site of adaptive ischemic intervention, PostC can be classified as in situ ischemic postconditioning (ISPostC) and remote ischemic postconditioning (RIPostC). Many studies have shown that ISPostC and RIPostC can reduce cerebral IS injury through protective mechanisms that increase cerebral blood flow after reperfusion, decrease antioxidant stress and anti-neuronal apoptosis, reduce brain edema, and regulate autophagy as well as Akt, MAPK, PKC, and KATP channel cell signaling pathways. However, few studies have compared the intervention methods, protective mechanisms, and cell signaling pathways of ISPostC and RIPostC interventions. Thus, in this article, we compare the history, common intervention methods, neuroprotective mechanisms, and cell signaling pathways of ISPostC and RIPostC.

Encéfalo/irrigação sanguínea , Pós-Condicionamento Isquêmico/métodos , Neuroproteção , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Transdução de Sinais/fisiologia
J Neurosci Methods ; 346: 108921, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32888963


BACKGROUND: Many studies have confirmed that "in situ ischemia postconditioning" (ISPostC) and "remote ischemic postconditioning" (RIPostC) can reduce cerebral ischemia/reperfusion injury, but there is no comparison was made on the consistency of neuroprotection in ISPostC and RIPostC to different ischemic duration and number of cycles. NEW METHOD: We used a transient middle cerebral artery occlusion model to compare the neuroprotection of ISPostC and RIPostC. We conducted ISPostC and RIPostC via brief and repeated MCA and Femoral artery occlusion followed by different ischemic duration and number of cycles. Infarct volume, brain edema, Neurological deficit scores and Apoptosis were evaluated. RESULTS: First, the ISPostC with three cycles of 10-s occlusion/30-s release of both carotid arteries and the RIPostC with three cycles of 10-min occlusion/10-min release of the left and right femoral arteries can obviously reduce cerebral infarction size, brain edema, apoptosis, and improve behavioral deficits than other approaches. Second, three cycles of ischemia/reperfusion may be the best for RIPostC. COMPARISON WITH EXISTING METHOD(S): In this paper, we compared different ischemic duration and frequency of ISPostC and RIPostC models to determine the best method. This conclusion helps to unify the experimental methods. CONCLUSIONS: Different ischemic duration and frequency of ischemic postconditioning affect neuroprotection. three cycles of 10-s occlusion/30-s release of both carotid arteries and three cycles of 10-min occlusion/10-min release of both femoral arteries could be the first choice to study mechanisms of ischemic postconditioning and be conducive to the unification of research results.

Isquemia Encefálica , Pós-Condicionamento Isquêmico , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Infarto da Artéria Cerebral Média/terapia , Neuroproteção , Ratos , Ratos Sprague-Dawley
CNS Neurol Disord Drug Targets ; 17(7): 547-556, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29992896


BACKGROUND & OBJECTIVE: Notoginsenoside R1 (NGR1) is one of the main effective components of Panax notoginseng. METHOD: Primary cortical neurons were harvested from neonatal rats and cultured to analyze the role of NGR1 in neuronal growth and the effects of NGR1 on the Wnt/ß-catenin signaling pathway. Following treatment with NGR1, immunocytochemistry was used to detect expression of Tuj1 and MAP2, and RT-qPCR was used to measure mRNA levels of key factors in the Wnt signaling pathway. RESULTS: Results showed that NGR1 promotes growth of cultured neurons and significantly upregulates mRNA levels of ß-catenin, Dishevelled, and Frizzled. To further confirm whether NGR1 promoted cortical neuron growth via the Wnt/ß-catenin signaling pathway, we knocked down ß- catenin mRNA by siRNA interference; following NGR1 treatment of ß-catenin-knockdown neurons, ß-catenin mRNA levels increased significantly. CONCLUSION: In conclusion, these results demonstrate that NGR1 promotes growth of cultured cortical neurons from the neonatal rat, possibly via the Wnt/ß-catenin signaling pathway.

Córtex Cerebral/citologia , Ginsenosídeos/farmacologia , Neurônios/efeitos dos fármacos , beta Catenina/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Animais , Animais Recém-Nascidos , Células Cultivadas , Relação Dose-Resposta a Droga , Embrião de Mamíferos , Ginsenosídeos/genética , Ginsenosídeos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/metabolismo , Técnicas de Patch-Clamp , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transfecção , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/genética