scholarly journals Tea Polysaccharide (TPS) Reduces Astrocytes Apoptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation by Regulating the miR-375/SRXN1 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ying Jiang ◽  
Hongmei Sun ◽  
Zhiqi Yin ◽  
Jun Yan
Keyword(s):  
Cerebral Ischemia ◽  
Cell Viability ◽  
Water Content ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Brain Water Content ◽  
Cerebral Ischemia Reperfusion ◽  
Brain Water

Objective. To investigate the effect of tea polysaccharides (TPS) mediated by miR-375/SRXN1 axis on mice with cerebral ischemia-reperfusion injury and proliferation and apoptosis of astrocytes (AS) conducted with oxygen-glucose deprivation/reoxygenation (OGD/R). Methods. Mouse model of middle cerebral artery occlusion (MCAO) and OGD/R-induced AS injury model were established; brain obstruction volume was measured by TTC staining; dry/wet weight ratio was used for measuring brain water content; hydrogen peroxide (H2O2) content in brain tissue was measured by H2O2 assay kit; cell viability and apoptosis rate were detected by MTT assay and flow cytometry, respectively; the expression level of miR-375 in OGD/R-AS was detected using qPCR; dual-luciferase reporter assay was used to verify the targeting relationship between miR-375 and SRXN1; mRNA levels of miR-375, SRXN1, Bcl-2, Bax, and caspase-3 were measured by qPCR; the protein levels of SRXN1, Bcl-2, Bax, and caspase-3 were measured by Western blotting. Results. The volume of cerebral obstruction, brain water content and H2O2 content in mice decreased gradually with the increase of TPS concentration. TPS treatment in vitro could effectively improve OGD/R-AS viability and reduce the apoptotic rate; overexpression of miR-375 inhibited AS viability but increased the apoptotic rate; TPS treatment resulted in a decrease in the expression of miR-375 in OGD/R-AS; MiR-375 targeted SRXN1 in AS; inhibition of miR-375 expression significantly upregulated SRXN1 levels; TPS treatment with simultaneous overexpression of SRXN1 significantly increased OGD/R-AS activity and reduced apoptosis; however, TPS treatment with simultaneous overexpression of SRXN1 and miR-375 resulted in no significant difference in cell viability and apoptosis rate compared with the control group. Conclusion. TPS reduces astrocyte injury induced by cerebral ischemia-reperfusion in mice by regulating the miR-375/SRXN1 molecular axis.

scholarly journals Neuroprotection of Sanhua Decoction against Focal Cerebral Ischemia/Reperfusion Injury in Rats through a Mechanism Targeting Aquaporin 4

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Lin Lu ◽  
Hui-qin Li ◽  
Ji-huang Li ◽  
Ai-ju Liu ◽  
Guo-qing Zheng
Keyword(s):  
Cerebral Ischemia ◽  
Water Content ◽  
Brain Edema ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Aquaporin 4 ◽  
Brain Water Content ◽  
Aqp4 Expression ◽  
Cerebral Ischemia Reperfusion ◽  
Brain Water

Sanhua decoction (SHD) is a famous classic Chinese herbal prescription for ischemic stroke, and aquaporin 4 (AQP4) is reported to play a key role in ischemic brain edema. This study aimed to investigate neuroprotection of SHD against focal cerebral ischemia/reperfusion (I/R) injury in rats and explore the hypothesis that AQP4 probably is the target of SHD neuroprotection against I/R rats. Lentiviral-mediated AQP4-siRNA was inducted into adult male Sprague-Dawley rats via intracerebroventricular injection. The focal cerebral ischemia/reperfusion model was established by occluding middle cerebral artery. Neurological examinations were performed according to Longa Scale. Brain water content, was determined by wet and dry weight measurement. Western blot was adopted to test the AQP4 expression in ipsilateral hippocampus. After the treatment, SHD alleviated neurological deficits, reduced brain water content and downregulated the expression of AQP4 at different time points following I/R injury. Furthermore, neurobehavioral function and brain edema after I/R were significantly attenuated via downregulation of AQP4 expression when combined with AQP4-siRNA technology. In conclusion, SHD exerted neuroprotection against focal cerebral I/R injury in rats mainly through a mechanism targeting AQP4.

Senescence marker protein 30 confers neuroprotection in oxygen-glucose deprivation/reoxygenation-injured neurons through modulation of Keap1/Nrf2 signaling: Role of SMP30 in OGD/R-induced neuronal injury

2020 ◽  
pp. 096032712095424
Author(s):  
Wenxiong Liu ◽  
Haikang Zhao ◽  
Yuqiang Su ◽  
Kefeng Wang ◽  
Jing Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Survival ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Marker Protein ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Senescence marker protein 30 (SMP30) is a senescence marker molecule and identified as a calcium regulatory protein. Currently, SMP30 has emerged as a cytoprotective protein in a wide range of cell types. However, the role of SMP30 in regulating neuronal survival during cerebral ischemia/reperfusion injury remains unclear. In the present study, we aimed to investigate the biological function and regulatory mechanism of SMP30 on neuronal survival using a cellular model induced by oxygen-glucose deprivation/reoxygenation (OGD/R). The results showed that SMP30 expression was significantly decreased by OGD/R exposure in neurons. Functional experiments demonstrated that SMP30 overexpression significantly rescued the decreased cell viability and attenuated the apoptosis and reactive oxygen species generation in OGD/R-exposed neurons. By contrast, SMP30 knockdown exhibited the opposite effect. Mechanism research revealed that SMP30 overexpression contributed to the activation of nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response element (ARE) signaling associated with downregulation of Kelch-like ECH-associated protein (Keap1). Keap1 overexpression or Nrf2 silencing significantly reversed SMP30-mediated neuroprotection against OGD/R-induced injury. Overall, these findings demonstrate that SMP30 overexpression protects neurons from OGD/R-induced apoptosis and oxidative stress by enhancing Nrf2/ARE antioxidant signaling via inhibition of Keap1. These data highlight the importance of the SMP30/Keap1/Nrf2/ARE signaling axis in regulating neuronal survival during cerebral ischemia/reperfusion injury.

Quercetin protects against cerebral ischemia/reperfusion and oxygen glucose deprivation/reoxygenation neurotoxicity

2020 ◽  
Vol 83 ◽  
pp. 108436 ◽  
Author(s):  
Ya-Yu Wang ◽  
Cheng-Yi Chang ◽  
Shih-Yi Lin ◽  
Jiaan-Der Wang ◽  
Chih-Cheng Wu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Cerebral Ischemia Reperfusion

scholarly journals Hsp20 Protects against Oxygen-Glucose Deprivation/Reperfusion-Induced Golgi Fragmentation and Apoptosis through Fas/FasL Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Bingwu Zhong ◽  
Zhiping Hu ◽  
Jieqiong Tan ◽  
Tonglin Lu ◽  
Qiang Lei ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Cerebral Ischemia Reperfusion ◽  
N2a Cells ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Golgi Fragmentation

Cerebral ischemia-reperfusion injury plays an important role in the development of tissue injury after acute ischemic stroke. Finding effective neuroprotective agents has become a priority in the treatment of ischemic stroke. The Golgi apparatus (GA) is a pivotal organelle and its protection is an attractive target in the treatment of cerebral ischemia-reperfusion injury. Protective effects of Hsp20, a potential cytoprotective agent due to its chaperone-like activity and involvement in regulation of many vital processes, on GA were assessed in an ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces Golgi fragmentation, apoptosis, and p115 cleavage in N2a cells. However, transfection with Hsp20 significantly attenuates OGDR-induced Golgi fragmentation and apoptosis. Hsp20 interacts with Bax, decreases FasL and Bax expression, and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. Our data demonstrate that increased Hsp20 expression protects against OGDR-induced Golgi fragmentation and apoptosis, likely through interaction with Bax and subsequent amelioration of the OGDR-induced elevation in p115 cleavage via the Fas/FasL signaling pathway. This neuroprotective potential of Hsp20 against OGDR insult and the underlying mechanism will pave the way for its potential clinical application for cerebral ischemia-reperfusion related disorders.

scholarly journals Molecular mechanisms for NG-nitro-L-arginine methyl ester action against cerebral ischemia–reperfusion injury-induced blood–brain barrier dysfunction

2014 ◽  
Vol 8 (2) ◽  
pp. 173-184
Author(s):  
Hanghui Wang ◽  
Yixin Song ◽  
Dingjun Hao ◽  
Lianfang Du
Keyword(s):  
Electron Microscope ◽  
Cerebral Ischemia ◽  
Methyl Ester ◽  
Evans Blue ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Brain Water Content ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Brain Water

Abstract Background: Ischemic stroke, an acute neurological injury lacking an effective therapy, is a leading cause of death worldwide. The unmet need in stroke research is to identify viable therapeutic targets and to understand their interplay during cerebral ischemia-reperfusion (I/R) injury. Objective: To explore the protective effects and molecular mechanism of NG-nitro-L-arginine methyl ester (L-NAME) in cerebral ischemia-reperfusion injury-induced blood-brain barrier (BBB) dysfunction. Methods: Two hundred fifty-six rats were randomly assigned to a sham operation group, I/R group, and I/R with L-NAME treatment group. Brain water content was determined by calculating dry/wet weight. The permeability of the BBB was observed using an electron microscope and by determining the Evans Blue leakage from brain tissue on the ischemic side. The expression of brain MMP-9 and GFAP was determined using an immunohistochemical method. The expression of ZO-1 protein was determined by western blotting. Results: We found that L-NAME remarkably attenuated the permeability of the BBB after I/R as assessed by Evans Blue leakage and brain water content (p < 0.05). This was further confirmed by examination of the ultrastructural morphology of the BBB using a transmission electron microscope. Furthermore, we found that expression of the zonae occludens-1 (ZO-1) was decreased in endothelial cells, and expression of MMP-9 and GFAP was increased in the basement membrane and astrocyte end-feet in vehicle control groups, respectively, but these changes could be prevented by L-NAME pretreatment. Conclusion: These results suggested that the neuroprotective effects of L-NAME against BBB damage induced by I/R might be related to the upregulation of tight junction proteins and inhibition of MMP-9 and GFAP expression. L-NAME can be used as a potential MMP-9-based multiple targeting therapeutic strategy in cerebral I/R injury.

scholarly journals LncRNA MALAT1 aggravates oxygen‐glucose deprivation/reoxygenation-induced neuronal endoplasmic reticulum stress and apoptosis via the miR-195a-5p/HMGA1 axis

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Ying Jia ◽  
Lian Yi ◽  
Qianqian Li ◽  
Tingjiao Liu ◽  
Shanshan Yang
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
High Mobility ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Background This study aimed to investigate the potential role and molecular mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in cerebral ischemia/reperfusion injury. Results Using an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, we determined that the expression of MALAT1 was significantly increased during OGD/R. MALAT1 knockdown reversed OGD/R-induced apoptosis and ER stress. Mechanistically, MALAT1 promoted OGD/R-induced neuronal injury through sponging miR-195a-5p to upregulating high mobility group AT-hook1 (HMGA1). Conclusions Collectively, these data demonstrate the mechanism underlying the invovlvement of MALAT1 in cerebral ischemia/reperfusion injury, thus providing translational evidence that MALAT1 may serve as a novel biomarker and therapeutic target for ischemic stroke.

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