Persistent High Levels of miR-502-5p Are Associated with Poor Neurologic Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage

Sheng, Bin; Fang, Xinggen; Liu, Cegang; Wu, Degang; Xia, Dayong; Xu, Shuo; Lai, Niansheng

doi:10.1016/j.wneu.2018.04.088

Cited by 19 publications

(17 citation statements)

References 24 publications

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“…SAH accounts for 5-7% of the total incidence of stroke [1,2]. A major prognostic determinant is the character of the initial hemorrhage that causes early brain injury (EBI) and early cerebral vasospasms (CVS) and may be associated with delayed cerebral ischemia (DCI) [3]. Several lines of evidence suggest that EBI after SAH may be the leading factor contributing to unfavorable outcomes following SAH [4,5].…”

Section: Introductionmentioning

confidence: 99%

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

Lai

Liang

et al. 2020

J Neuroinflammation

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Background: Inflammation is a potential crucial factor in the pathogenesis of subarachnoid hemorrhage (SAH). Circulating microRNAs (miRNAs) are involved in the regulation of diverse aspects of neuronal dysfunction. The therapeutic potential of miRNAs has been demonstrated in several CNS disorders and is thought to involve modulation of neuroinflammation. Here, we found that peripherally injected modified exosomes (Exos) delivered miRNAs to the brains of mice with SAH and that the potential mechanism was regulated by regulation of neuroinflammation. Methods: Next-generation sequencing (NGS) and qRT-PCR were used to define the global miRNA profile of plasma exosomes in aSAH patients and healthy controls. We peripherally injected RVG/Exos/miR-193b-3p to achieve delivery of miR-193b-3p to the brain of mice with SAH. The effects of miR-193b-3p on SAH were assayed using a neurological score, brain water content, blood-brain barrier (BBB) injury, and Fluoro-Jade C (FJC) staining. Western blotting analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to measure various proteins and mRNA levels. Results: NGS and qRT-PCR revealed that four circulating exosomal miRNAs were differentially expressed. RVG/Exos exhibited improved targeting to the brains of SAH mice. MiR-193b-3p suppressed the expression and activity of HDAC3, upregulating the acetylation of NF-κB p65. Finally, miR-193b-3p treatment mitigated the neurological behavioral impairment, brain edema, BBB injury, and neurodegeneration induced by SAH, and reduced inflammatory cytokine expression in the brains of mice after SAH. Conclusions: Exos/miR-193b-3p treatment attenuated the inflammatory response by acetylation of the NF-κB p65 via suppressed expression and activity of HDAC3. These effects alleviated neurobehavioral impairments and neuroinflammation following SAH.

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Section: Introductionmentioning

confidence: 99%

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

Lai

Liang

et al. 2020

J Neuroinflammation

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123

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“…The potential of miRNAs serving as biomarkers for aSAH complications was recently explored in several reports (Su et al, 2015;Powers et al, 2016;Bache et al, 2017;Kikkawa et al, 2017;Lu et al, 2017;Stylli et al, 2017;Lopes et al, 2018; -Nicolas et al, 2018;Sheng et al, 2018a). These studies confirmed that dysregulated miRNA expression is associated with aSAH and its acute complications, which could be observed in extracellular fluids.…”

Section: Discussionmentioning

confidence: 76%

A Highly Predictive MicroRNA Panel for Determining Delayed Cerebral Vasospasm Risk Following Aneurysmal Subarachnoid Hemorrhage

Wang

Springer

Xie

et al. 2021

Front. Mol. Biosci.

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Approximately one-third of aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral vasospasm (DCV) 3–10 days after aneurysm rupture resulting in additional, permanent neurologic disability. Currently, no validated biomarker is available to determine the risk of DCV in aSAH patients. MicroRNAs (miRNAs) have been implicated in virtually all human diseases, including aSAH, and are found in extracellular biofluids including plasma and cerebrospinal fluid (CSF). We used a custom designed TaqMan Low Density Array miRNA panel to examine the levels of 47 selected brain and vasculature injury related miRNAs in CSF and plasma specimens collected from 31 patients with or without DCV at 3 and 7 days after aSAH, as well as from eight healthy controls. The analysis of the first 18-patient cohort revealed a striking differential expression pattern of the selected miRNAs in CSF and plasma of aSAH patients with DCV from those without DCV. Importantly, this differential expression was observed at the early time point (3 days after aSAH), before DCV event occurs. Seven miRNAs were identified as reliable DCV risk predictors along with a prediction model constructed based on an array of additional 19 miRNAs on the panel. These chosen miRNAs were then used to predict the risk of DCV in a separate, testing cohort of 15 patients. The accuracy of DCV risk prediction in the testing cohort reached 87%. The study demonstrates that our novel designed miRNA panel is an effective predictor of DCV risk and has strong applications in clinical management of aSAH patients.

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“…Many studies have shown that there is a close relationship between SAH and miRNA in a variety of physiological and pathological aspects, such as signal pathway level, cellular level, and so on, and predict that miRNA will become one of the effective methods for the treatment of SAH in the future ( Su et al, 2015 ; Chen et al, 2017 ). It not only participates in inflammation, neuronal apoptosis, synaptic remodeling, and many other cellular functions but also detects the differential expression of miRNA in blood, cerebrospinal fluid (CSF) of SAH patients, and MCA of SAH model in rats ( Kikkawa et al, 2017 ; Sheng et al, 2018a , b ). Many disorders of miRNA expression are involved in the occurrence and development of CVS, and the detection of miRNA in EVs can be used as a new standard to prevent, diagnose, and judge the prognosis of CVS after SAH.…”

Section: Discussionmentioning

confidence: 99%

miRNA Profiling of Circulating Small Extracellular Vesicles From Subarachnoid Hemorrhage Rats Using Next-Generation Sequencing

Lan

Zhou

Wang

et al. 2020

Front. Cell. Neurosci.

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Background: Extracellular vesicles (EVs) are produced during abnormal and normal physiological conditions. Understanding the expression profile of microRNA (miRNA) in plasma-derived small extracellular vesicles (sEVs) and their roles in subarachnoid hemorrhage (SAH) that cause cerebral vasospasm (CVS) is imperative. Methods: Sprague Dawley rats (250-300 g) were allocated to sham or SAH groups established using endovascular perforation method. miRNA expression profiles of plasma sEVs in both groups (each n = 4) were evaluated using next-generation sequencing (NGS). Results: There were 142 microRNAs (miRNAs) significantly expressed differently between the two groups, of which 73 were up-regulated while 69 were down-regulated in SAH sEVs compared with those of sham (p < 0.05; fold change ≥ 2). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses of differently expressed (DE) miRNAs revealed signaling pathways and target genes (TGs) in the SAH group. rno-miR-185-5p, rno-miR-103-3p, rno-miR-15b-3p, rno-miR-93-5p, and rno-miR-98-5p were the top five most up-regulated sEVs miRNAs. Conclusion: Our results suggest that miRNA can be selectively packaged into sEVs under SAH, and this could help develop potential targets for the prevention, diagnosis, and treatment of CVS after this condition.

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Persistent High Levels of miR-502-5p Are Associated with Poor Neurologic Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage

Cited by 19 publications

References 24 publications

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

A Highly Predictive MicroRNA Panel for Determining Delayed Cerebral Vasospasm Risk Following Aneurysmal Subarachnoid Hemorrhage

miRNA Profiling of Circulating Small Extracellular Vesicles From Subarachnoid Hemorrhage Rats Using Next-Generation Sequencing

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