scholarly journals Overexpression of MicroRNA-145 Ameliorates Astrocyte Injury by Targeting Aquaporin 4 in Cerebral Ischemic Stroke

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Lifang Zheng ◽  
Wei Cheng ◽  
Xijia Wang ◽  
Zhigang Yang ◽  
Xiangling Zhou ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Ischemic Injury ◽  
Glucose Deprivation ◽  
Expression Levels ◽  
Cultured Astrocytes ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic ◽  
Induced Apoptosis ◽  
Global Population

Cerebral ischemic stroke, which affects the global population, is a major disease with high incidence, mortality, and disability. Accumulating evidence has indicated that abnormal microRNA (miRNA) expression plays essential roles in the pathologies of ischemic stroke. Yet, the underlying regulatory mechanism of miRNAs in cerebral ischemic stroke remains unclear. We investigated the role of miR-145 in cerebral ischemic stroke and its potential mechanism in a model using primary cultured astrocytes. We detected the expression levels of miR-145 and its target gene AQP4 and assessed the role of miR-145 in cell death and apoptosis caused by oxygen-glucose deprivation (OGD). Bioinformatics analysis was used to explore the targets of miR-145. miR-145 expression levels were significantly decreased in primary astrocytes subjected to OGD. miR-145 overexpression promoted astrocyte health and inhibited OGD-induced apoptosis. AQP4 was a direct target of miR-145, and miR-145 suppressed AQP4 expression. Moreover, AQP4 enhanced astrocyte injury in ischemic stroke, and AQP4 knockdown diminished the miR-145-mediated protective effect on ischemic injury. Taken together, our results show that miR-145 plays an important role in protecting astrocytes from ischemic injury by downregulating AQP4 expression. These findings may highlight a novel therapeutic target in cerebral ischemic stroke.

scholarly journals The evolving role of neuro-immune interaction in brain repair after cerebral ischemic stroke

2018 ◽  
Vol 24 (12) ◽  
pp. 1100-1114 ◽  
Author(s):  
Xin Wang ◽  
Wei Xuan ◽  
Zi-Yu Zhu ◽  
Yan Li ◽  
Hao Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Repair ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

cGAS-STING signaling regulates control of microglia polarization in cerebral ischemic stroke

2020 ◽  
Author(s):  
Guoliang Jiang ◽  
Xinglong Yang ◽  
Houjun Zhou ◽  
Jiang Long ◽  
Linming Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Inflammatory Response ◽  
Cell Model ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Ht22 Cells ◽  
Bv2 Microglia ◽  
Cerebral Ischemic Stroke ◽  
Sting Pathway ◽  
Cerebral Ischemic

Abstract Background Cerebral ischemic stroke is a highly debilitating disease, in which inflammation is well document to play a pivotal role in its pathophysiology. Microglia are the the major immuncompetent cells of the brain involved in different neuropathologies. Recent discovery of cyclic GMP-AMP synthase(cGAS) activation and its induction of the downstream signaling protein stimulator of interferon genes (STING) is increasingly recognized as a crucial determinant of neuropathophysiology. Although cGAS-STING pathway has been reported to play an important role in inflammatory response in myocardial infarction (MI), its mechanism in inflammatory response in ischemic stroke (IS) has remained to be fully explored.Methods In light of the above, this study sought to explore the roles of cGAS-STING pathway in inflammatory reaction in IS. It is hoped that the results would provide new insights for designing of therapeutic strategies targeting at IS. We used HT22 cells to establish an oxygen-glucose deprivation (OGD) cell model. The supernatant derived from this and which contained OGD-induced DAMPs(OIDs) was used to stimulate the BV2 microglia. Additionally, we used siRNA technology to interfere with cGAS gene expression to observe changes in downstream cytokines. Furthermore, we established middle cerebral artery occlusion (MCAO) mouse model and performed cGAS-siRNA lentivirus infection to further elucidate the mechanism of cGAS-STING pathway in vivo.Results We show here that OIDs strongly activated the cGAS-STING pathway and triggered accumulation of a plethora of proinflammatory factors in activated Microglia. Of note, the cascade reaction was successfully inhibited by cGAS-siRNA. Furthermore, we extended the study of cGAS-STING in a mouse MCAO model, which showed that inhibiting cGAS-STING pathway can effectively diminish MIDs(MCAO-induced DAMPs)-induced neuronal apoptosis and ultimately functional improvement.Conclusion The present results have shown GAS-STING signaling pathway controls the polarity transformation of microglia. The underlying mechanisms of cGAS-STING triggering microglial inflammatory response is now better clarified which made the pathway a potential therapeutic target of IS.

scholarly journals Role of angiogenesis in patients with cerebral ischemic stroke.

Stroke ◽  
1994 ◽  
Vol 25 (9) ◽  
pp. 1794-1798 ◽  
Author(s):  
J Krupinski ◽  
J Kaluza ◽  
P Kumar ◽  
S Kumar ◽  
J M Wang
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

The Role of Exogenous Neural Stem Cells Transplantation in Cerebral Ischemic Stroke

2014 ◽  
Vol 10 (11) ◽  
pp. 3219-3230 ◽  
Author(s):  
Lukui Chen ◽  
Rong Qiu ◽  
Lushen Li ◽  
Dan He ◽  
Haiqin Lv ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ischemic Stroke ◽  
Neural Stem Cells ◽  
Stem Cells Transplantation ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

scholarly journals The role of KATP channels in cerebral ischemic stroke and diabetes

2018 ◽  
Vol 39 (5) ◽  
pp. 683-694 ◽  
Author(s):  
Vivian Szeto ◽  
Nai-hong Chen ◽  
Hong-shuo Sun ◽  
Zhong-ping Feng
Keyword(s):  
Ischemic Stroke ◽  
Katp Channels ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

scholarly journals Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke

2017 ◽  
Vol 43 (1) ◽  
pp. 182-194 ◽  
Author(s):  
Dong Guo ◽  
Ji Ma ◽  
Lei Yan ◽  
Tengfei Li ◽  
Zhiguo Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Injury ◽  
Down Regulation ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Background/Aims: LncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported to be highly expressed in an in vitro mimic of ischemic stroke conditions. However, the exact biological role of MALAT1 and its underlying mechanism in ischemic stroke remain to be elucidated. Methods: The roles of MALAT1 and miR-30a on cell death and infarct volume and autophagy were evaluated in experimental ischemic stroke. The relationships between miR-30a and MALAT1, Beclin1 were confirmed by luciferase reporter assay. The autophagy inhibitor 3-methyadenine (3-MA) was used to examine the impact of autophagy on ischemic injury. Results: We found that MALAT1, along with the levels of conversion from autophagy-related protein microtubule-associated protein light chain 3-I (LC3-I) to LC3-phosphatidylethanolamine conjugate (LC3-II), as well as Beclin1 were up-regulated and miR-30a was down-regulated in cerebral cortex neurons after oxygen-glucose deprivation (OGD) and mouse brain cortex after middle cerebral artery occlusion-reperfusion (MCAO). Down-regulation of MALAT1 suppressed ischemic injury and autophagy in vitro and in vivo. Furthermore, MALAT1 may serve as a molecular sponge for miR-30a and negatively regulate its expression. In addition, MALAT1 overturned the inhibitory effect of miR-30a on ischemic injury and autophagy in vitro and in vivo, which might be involved in the derepression of Beclin1, a direct target of miR-30a. Mechanistic analyses further revealed that autophagy inhibitor 3-methyadenine (3-MA) markedly suppressed OGD-induced neuronal cell death and MCAO-induced ischemic brain infarction. Conclusion: Taken together, our study first revealed that down-regulation of MALAT1 attenuated neuronal cell death through suppressing Beclin1-dependent autophagy by regulating miR-30a expression in cerebral ischemic stroke. Besides, our study demonstrated a novel lncRNA-miRNA-mRNA regulatory network that is MALAT1-miR-30a-Beclin1 in ischemic stroke, contributing to a better understanding the pathogenesis and progression of ischemic stroke.

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