A blockade of microRNA-155 signal pathway has a beneficial effect on neural injury after intracerebral haemorrhage via reduction in neuroinflammation and oxidative stress

Zhang, Wenwen; Wang, Luping; Wang, Ruimin; Duan, Zongsheng; Wang, Hushan

doi:10.1080/13813455.2020.1764047

Cited by 12 publications

(9 citation statements)

References 52 publications

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“…Among these microRNAs, miR-155 is identified as an important regulatory component of circadian function and is related to various pathophysiological processes involved in oxidative stress and neuroinflammation, including controlling the production of inflammatory cytokines (19,50). Moreover, Zhang et al reported that there was a striking increase in miR-155 levels after ICH, and antagomir-155 attenuated neural injury after ICH by reducing inflammation and oxidative stress (20). According to previous reports, miR-155 is a critical posttranscriptional repressor of Bmal1 in macrophages and endothelial cells (19,51).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, miR-155 may regulate Bmal1 mRNA stability and translation. Moreover, a previous study suggested that strategies targeting miR-155 and its downstream signaling pathway exerted a beneficial effect on SBI induced by ICH (20). Nevertheless, researchers have not clearly determined whether antagomir-155 upregulates BMAL1 expression and subsequently attenuates ICH-induced brain injury in rats.…”

Section: Introductionmentioning

confidence: 99%

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BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

Gong¹,

Zhang²,

Li³

et al. 2021

Ann Transl Med

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Background: Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with high morbidity and mortality rates. Oxidative stress and inflammation are important pathological mechanisms of secondary brain injury (SBI) after ICH. Brain and muscle Arnt-like protein 1 (BMAL1), which forms the core component of the circadian clock, was previously shown to be involved in many diseases and to participate in oxidative stress and inflammatory responses. However, the role of BMAL1 in SBI following ICH is unknown. In addition, treatments targeting miR-155 and its downstream signaling pathway may exert a beneficial effect on SBI after ICH, while miR-155 may regulate Bmal1 mRNA stability and translation. Nevertheless, researchers have not clearly determined whetheantagomir-155 upregulates BMAL1 expression and subsequently attenuates ICHinduced brain injury in rats.Methods: After establishing an ICH rat model by injecting autologous blood, the time course of changes in levels of the BMAL1 protein after ICH was analyzed. Subsequently, this study was designed to investigate the potential role and mechanisms of BMAL1 in SBI following ICH using lentiviral overexpression and antagomir-155 treatments.Results: BMAL1 protein levels were significantly decreased in the ICH group compared to the sham group. Genetic overexpression of BMAL1 alleviated oxidative stress, inflammation, brain edema, bloodbrain barrier injury, neuronal death, and neurological dysfunction induced by ICH. On the other hand, we observed that inhibiting miRNA-155 using antagomir-155 promoted the expression of BMAL1 and further activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway to attenuate brain injury after ICH.Conclusions: These results reveal that BMAL1 serves as a neuroprotective agent in ICH and upregulation of BMAL1 attenuates ICH-induced SBI. Therefore, BMAL1 may be a promising therapeutic target for SBI following ICH.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

Gong¹,

Zhang²,

Li³

et al. 2021

Ann Transl Med

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“…Recently, miR-367 was described to regulate IRAK4 in primary microglia cells that negatively modulated the inflammatory response of microglia in an intracerebral hemorrhage [33]. Based on an animal model of an intracerebral hemorrhage, the levels of miR-155 were amplified in different parts of the CNS and this alteration was accompanied by increases of IL-1β, IL-6, and TNF-α, thus blocking the central miR-155 pathway, which may play a beneficial role in regulating neurological function [34]. Taken together, further studies are required to reveal additional cellular mechanisms in the development of IVH-mediated inflammation.…”

Section: Discussionmentioning

confidence: 99%

Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells

Fejes

Pócsi

Takai

et al. 2021

IJMS

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Following an intraventricular hemorrhage (IVH), red blood cell lysis and hemoglobin (Hb) oxidation with the release of heme can cause sterile neuroinflammation. In this study, we measured Hb derivates and cellular adhesion molecules ICAM-1 and VCAM-1 with cell-free miRNAs in cerebrospinal fluid (CSF) samples obtained from Grade-III and Grade-IV preterm IVH infants (IVH-III and IVH-IV, respectively) at multiple time points between days 0–60 after the onset of IVH. Furthermore, human choroid plexus epithelial cells (HCPEpiCs) were incubated with IVH and non-IVH CSF (10 v/v %) for 24 h in vitro to investigate the IVH-induced inflammatory response that was investigated via: (i) HMOX1, IL8, VCAM1, and ICAM1 mRNAs as well as miR-155, miR-223, and miR-181b levels by RT-qPCR; (ii) nuclear translocation of the NF-κB p65 subunit by fluorescence microscopy; and (iii) reactive oxygen species (ROS) measurement. We found a time-dependent alteration of heme, IL-8, and adhesion molecules which revealed a prolonged elevation in IVH-IV vs. IVH-III with higher miR-155 and miR-181b expression at days 41–60. Exposure of HCPEpiCs to IVH CSF samples induced HMOX1, IL8, and ICAM1 mRNA levels along with increased ROS production via the NF-κB pathway activation but without cell death, as confirmed by the cell viability assay. Additionally, the enhanced intracellular miR-155 level was accompanied by lower miR-223 and miR-181b expression in HCPEpiCs after CSF treatment. Overall, choroid plexus epithelial cells exhibit an abnormal cell phenotype after interaction with pro-inflammatory CSF of IVH origin which may contribute to the development of later clinical complications in preterm IVH.

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“…Furthermore, dexamethasone-mediated attenuation of the expression of proinflammatory cytokines such as IFN-β, IL-6, and TNF-α after ICH in mice was associated with a reduction in miR-155, implicating its role in neuroinflammation [ 50 ]. Moreover, a recent preclinical study reported the efficacy of miR-155 inhibitors in improving acute neurological outcomes after ICH [ 51 ]. In line with this observation, the genetic inhibition of miR-155 attenuated ischemic brain damage with a reduction in the release of proinflammatory cytokines in a mouse model of MCAO and attenuated glucose deprivation/oxygenation-induced proinflammatory cytokine expression in vitro [ 52 ].…”

Section: Microrna and Ich-induced Neuroinflammationmentioning

confidence: 99%

Dysregulation of microRNA and Intracerebral Hemorrhage: Roles in Neuroinflammation

Kashif

Shah

Sukumari‐Ramesh

2021

IJMS

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Intracerebral hemorrhage (ICH) is a major public health problem and devastating subtype of stroke with high morbidity and mortality. Notably, there is no effective treatment for ICH. Neuroinflammation, a pathological hallmark of ICH, contributes to both brain injury and repair and hence, it is regarded as a potential target for therapeutic intervention. Recent studies document that microRNAs, small non-coding RNA molecules, can regulate inflammatory brain response after ICH and are viable molecular targets to alter brain function. Therefore, there is an escalating interest in studying the role of microRNAs in the pathophysiology of ICH. Herein, we provide, for the first time, an overview of the microRNAs that play roles in ICH-induced neuroinflammation and identify the critical knowledge gap in the field, as it would help design future studies.

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A blockade of microRNA-155 signal pathway has a beneficial effect on neural injury after intracerebral haemorrhage via reduction in neuroinflammation and oxidative stress

Cited by 12 publications

References 52 publications

BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells

Dysregulation of microRNA and Intracerebral Hemorrhage: Roles in Neuroinflammation

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