Non-coding RNAs and neuroprotection after acute CNS injuries

Chandran, Raghavendar; Mehta, Suresh L.

doi:10.1016/j.neuint.2017.01.015

Cited by 89 publications

(63 citation statements)

References 187 publications

(232 reference statements)

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“…LncRNAs are a newly discovered class of regulators in the cerebral vascular endothelium after ischemic injury, such as stroke [29]. In recent years, non-coding RNAs have emerged as novel targets to treat ischemia stroke [30,31]. For example, inhibition of LncCHRF reduced ischemic injury by regulating the miR-126/SOX6 axis [32].…”

Section: Discussionmentioning

confidence: 99%

LncRNA MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145 to regulate AQP4

et al. 2020

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Background: The present study aimed to verify whether long noncoding RNA (lncRNA) MALAT1 is involved in brain tissue damage induced by ischemia-reperfusion injury, and to explore the mechanism by which MALAT1 regulates aquaporin 4 (AQP4). Methods: In this study, we established glucose deprivation (OGD)/reoxygenation (RX) astrocyte cell model and middle cerebral artery occlusion (MCAO)/reperfusion mouse model in vitro and in vivo. Then cell counting kit-8 assay, flow cytometry analysis, Triphenyltetrazolium chloride (TTC) staining, and western blotting were used to determine cell viability, cell apoptosis, cerebral infarction volume, and the abundance of AQP4, respectively. Results:We found that the level of MALAT1 was significantly upregulated in both the MCAO/reperfusion model and OGD/RX model. Knockdown of MALAT1 increased cell viability and reduced cell apoptosis in MA-C cells, while an AQP4 siRNA combined with a siRNA targeting MALAT1 could not enhance this effect. Further experiments showed that MALAT1 positively regulated AQP4 expression via miR-145. The MALAT1 siRNA did not alleviate the exacerbation of damage after miR-145 inhibitor action. However, an miR-145 inhibitor reversed the protection effects of MALAT1, indicating that MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145. TTC staining showed that the infracted area of whole brain was significantly attenuated in treated with sh-MALAT1 group in vivo. Conclusion:Taken together, our study confirmed that MALAT1 promotes cerebral ischemia-reperfusion injury by affecting AQP4 expression through competitively binding miR-145, indicating that MALAT1 might be a new therapeutic target for treatment cerebral ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

LncRNA MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145 to regulate AQP4

et al. 2020

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“…A full accounting of the potential role of miRNAs as therapeutic targets or agents for ischemic stroke is beyond the scope of our review and the reader is referred to some recent articles on the topic (Chandran et al, 2017; Gaudet et al, 2017; Kaur et al, 2018; Khoshnam et al, 2017). Rather, we focus on several miRNAs that have garnered considerable interest and are illustrative of the potential benefits and challenges of this approach.…”

Section: Recently Identified Molecular/cellular Targets and Approachesmentioning

confidence: 99%

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

Shekhar

Cunningham

Pabbidi

et al. 2018

European Journal of Pharmacology

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Ischemic stroke is a devastating and debilitating medical condition with limited therapeutic options. However, accumulating evidence indicates a central role of inflammation in all aspects of stroke including its initiation, the progression of injury, and recovery or wound healing. A central target of inflammation is disruption of the blood brain barrier or neurovascular unit. Here we discuss recent developments in identifying potential molecular targets and immunomodulatory approaches to preserve or protect barrier function and limit infarct damage and functional impairment. These include blocking harmful inflammatory signaling in endothelial cells, microglia/macrophages, or Th17/γδ T cells with biologics, third generation epoxyeicosatrienoic acid (EET) analogs with extended half-life, and miRNA antagomirs. Complementary beneficial pathways may be enhanced by miRNA mimetics or hyperbaric oxygenation. These immunomodulatory approaches could be used to greatly expand the therapeutic window for thrombolytic treatment with tissue plasminogen activator (t-PA). Moreover, nanoparticle technology allows for the selective targeting of endothelial cells for delivery of DNA/RNA oligonucleotides and neuroprotective drugs. In addition, although likely detrimental to the progression of ischemic stroke by inducing inflammation, oxidative stress, and neuronal cell death, 20-HETE may also reduce susceptibility of onset of ischemic stroke by maintaining autoregulation of cerebral blood flow. Although the interaction between inflammation and stroke is multifaceted, a better understanding of the mechanisms behind the pro-inflammatory state at all stages will hopefully help in developing novel immunomodulatory approaches to improve mortality and functional outcome of those inflicted with ischemic stroke.

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“…Nitrosative stress may lead to BBB breakdown, inflammation, and caspase activation, which ultimately lead to cell apoptosis through interacting with different cellular signaling pathways including matrix metalloproteinase, high-mobility group box 1, toll-like receptors 2 and 4, poly(ADP-ribose) polymerase, Src, Rhoassociated protein kinase (ROCK), and glycogen synthase kinase (GSK)-3β (Radi et al, 2015). Oxidative stress may also influence epigenetic mechanisms (i.e., DNA methylation, histone modification, microRNAs) (Zhao et al, 2016;Narne et al, 2017), well known to be implicated in neuroprotection (Felling and Song, 2015;Simon, 2016;Chandran et al, 2017). Therefore, it has been suggested that ROS may contribute themselves to neuronal recovery after ischemic stroke.…”

Section: Hausenloy Et Al 2014mentioning

confidence: 99%

Neutrophil-Related Oxidants Drive Heart and Brain Remodeling After Ischemia/Reperfusion Injury

2020

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The inflammatory response associated with myocardial and brain ischemia/reperfusion injury (IRI) is a critical determinant of tissue necrosis, functional organ recovery, and long-term clinical outcomes. In the post-ischemic period, reactive oxygen species (ROS) are involved in tissue repair through the clearance of dead cells and cellular debris. Neutrophils play a critical role in redox signaling due to their early recruitment and the large variety of released ROS. Noteworthy, ROS generated during IRI have a relevant role in both myocardial healing and activation of neuroprotective pathways. Anatomical and functional differences contribute to the responses in the myocardial and brain tissue despite a significant gene overlap. The exaggerated activation of this signaling system can result in adverse consequences, such as cell apoptosis and extracellular matrix degradation. In light of that, blocking the ROS cascade might have a therapeutic implication for cardiomyocyte and neuronal loss after acute ischemic events. The translation of these findings from preclinical models to clinical trials has so far failed because of differences between humans and animals, difficulty of agents to penetrate into specific cellular organs, and specifically unravel oxidant and antioxidant pathways. Here, we update knowledge on ROS cascade in IRI, focusing on the role of neutrophils. We discuss evidence of ROS blockade as a therapeutic approach for myocardial infarction and ischemic stroke.

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Non-coding RNAs and neuroprotection after acute CNS injuries

Cited by 89 publications

References 187 publications

LncRNA MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145 to regulate AQP4

LncRNA MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145 to regulate AQP4

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

Neutrophil-Related Oxidants Drive Heart and Brain Remodeling After Ischemia/Reperfusion Injury

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