Changes in Whole-Blood microRNA Profiles during the Onset and Treatment Process of Cerebral Infarction: A Human Study

Abe, Arata; Tanaka, Mayui; Yasuoka, Akihito; Saito, Yoshikazu; Okada, Shinji; Mishina, Masayoshi; Abe, Keiko; Kimura, Kazumi; Asakura, Tomiko

doi:10.3390/ijms21093107

Cited by 13 publications

(10 citation statements)

References 28 publications

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“…Its levels were significantly increased in patients with moderate-severe stroke ( n = 65) compared to control patients, but not in minor stroke ( n = 67) compared to control patients [ 58 ]. Furthermore, in another study among ischemic stroke patients ( n = 22), elevated plasma levels of the X-linked miR-505 differentiated stroke patients from controls ( n = 22) and its levels normalized following stroke treatment [ 118 ]. Regarding stroke triggered by large or small-artery occlusion, decreased X-linked miR-221 levels were observed among patients with ischemic stroke ( n = 46) [ 90 ].…”

Section: Actual and Potential Clinical Implicationsmentioning

confidence: 99%

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

Florijn

Bijkerk

Kruyt

et al. 2021

IJMS

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Accumulating evidence pinpoints sex differences in stroke incidence, etiology and outcome. Therefore, more understanding of the sex-specific mechanisms that lead to ischemic stroke and aggravation of secondary damage after stroke is needed. Our current mechanistic understanding of cerebral ischemia states that endothelial quiescence in neurovascular units (NVUs) is a major physiological parameter affecting the cellular response to neuron, astrocyte and vascular smooth muscle cell (VSMC) injury. Although a hallmark of the response to injury in these cells is transcriptional activation, noncoding RNAs such as microRNAs exhibit cell-type and context dependent regulation of gene expression at the post-transcriptional level. This review assesses whether sex-specific microRNA expression (either derived from X-chromosome loci following incomplete X-chromosome inactivation or regulated by estrogen in their biogenesis) in these cells controls NVU quiescence, and as such, could differentiate stroke pathophysiology in women compared to men. Their adverse expression was found to decrease tight junction affinity in endothelial cells and activate VSMC proliferation, while their regulation of paracrine astrocyte signaling was shown to neutralize sex-specific apoptotic pathways in neurons. As such, these microRNAs have cell type-specific functions in astrocytes and vascular cells which act on one another, thereby affecting the cell viability of neurons. Furthermore, these microRNAs display actual and potential clinical implications as diagnostic and prognostic biomarkers in ischemic stroke and in predicting therapeutic response to antiplatelet therapy. In conclusion, this review improves the current mechanistic understanding of the molecular mechanisms leading to ischemic stroke in women and highlights the clinical promise of sex-specific microRNAs as novel diagnostic biomarkers for (silent) ischemic stroke.

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Section: Actual and Potential Clinical Implicationsmentioning

confidence: 99%

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

Florijn

Bijkerk

Kruyt

et al. 2021

IJMS

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“…Cerebral infarction is a common brain disease in neurology clinically that is common in middle-aged and elderly people, which is characterized by a high disability rate and mortality rate. 12 The mortality of acute cerebral infarction has been reported to be 5% - 15%. 13 Weaver et al 14 revealed in their research that there was a high risk of cognitive impairment (about 50%) even after effective treatment.…”

Section: Discussionmentioning

confidence: 99%

Effect of Butylphthalide combined with Oxiracetam on cognitive function, Intellectual recovery and serum inflammatory factors in patients with cognitive impairment after cerebral infarction

Jiang¹,

Yu²,

Deng³

2023

Pak J Med Sci

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Objective: To evaluate the effect of butylphthalide combined with oxiracetam on cognitive function, intellectual recovery and serum inflammatory factors in patients with cognitive impairment after cerebral infarction. Methods: This is a Clinical comparative study. A total of 80 patients with cognitive impairment after cerebral infarction who visited Renmin Hospital, Hubei University of Medicine from January 2020 to January 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with oral oxiracetam combined with routine treatment. Patients in the study group were given butylphthalide combined with oxiracetam on the basis of routine treatment. Compare the clinical effect, cognitive function and intellectual recovery, inflammatory factor level changes, CBV, CBF, MTT and other cerebral blood flow perfusion indicators, as well as post-treatment incidence of adverse drug reactions in the two groups of patients. Results: The efficacy of the study group was significantly higher than that of the control group (p=0.03). After treatment, the levels of CBV and CBF in the study group were higher than those in the control group, the levels of TNF-α, CRP and IL-6 were significantly lower than those of the control group, while MTT was shorter than that in the control group, with statistically significant difference (p=0.00). Furthermore, there was a statistically significant difference that the MMSE score and MOCA score of the study group were higher than those of the control group (p=0.00). Conclusion: Butylphthalide combined with oxiracetam has an obvious curative effect in the treatment of patients with cognitive impairment after cerebral infarction. It is a safe and effective therapeutic option that can significantly recover cognitive function and intelligence, improve cerebral blood flow perfusion and reduce inflammatory factors, without an obvious increase in adverse reactions. doi: https://doi.org/10.12669/pjms.39.2.6901 How to cite this: Jiang W, Yu X, Deng Y. Effect of Butylphthalide combined with Oxiracetam on cognitive function, Intellectual recovery and serum inflammatory factors in patients with cognitive impairment after cerebral infarction. Pak J Med Sci. 2023;39(2):---------. doi: https://doi.org/10.12669/pjms.39.2.6901 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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“…A large clinical study found that 7 miRNAs were significantly associated with cerebrovascular disorder and a model of 3 miRNAs combination could predict the risk of stroke ( Sonoda et al, 2019 ). Another clinical study involving 22 AIS patients and 6 AIS patients received treatment demonstrated that miRNAs altered during the onset and treatment and possessed potential value for predicting symptom progression after stroke ( Abe et al, 2020 ). In line with these studies, we observe that a higher neutrophilic miRNA-23a level is associated with moderate-to-severe stroke on admission and symptom improvement at 24 h after rtPA treatment, and the noncoding RNA score composed of miRNA-23a, miRNA-99a, and lncRNA H19 is associated with the infarct volume and symptom progression at 7 days after rtPA treatment.…”

Section: Discussionmentioning

confidence: 99%

Neutrophilic noncoding RNAs predict outcomes of acute ischemic stroke patients treated with recombinant tissue plasminogen activator

Han

Tao

et al. 2022

Front. Pharmacol.

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There’s no evidence demonstrating the association between noncoding RNAs levels before IV recombinant tissue plasminogen activator (rtPA) administration and the outcomes of acute ischemic stroke (AIS). 145 AIS patients received rtPA treatment were recruited at the stroke center from 2018 to 2019, and 103 patients were included in this study. A panel of noncoding RNAs (miRNA-23a, miRNA-193a, miRNA-128, miRNA-99a, miRNA-let-7a, miRNA-494, miRNA-424, and lncRNA H19) were measured in the circulating neutrophils of AIS patients before rtPA treatment. Endpoints included excellent outcome (modified Rankin Scale score [mRS] 0–1) or poor outcome (mRS > 1) at 3 months and symptomatic intracerebral hemorrhage (sICH) after rtPA treatment. Among the eight noncoding RNAs detected in circulating neutrophils of the 103 participants, miRNA-23a levels were associated with the stroke severity on admission and symptom progression at 24 h after rtPA treatment. A noncoding RNA score composed of miRNA-23a, miRNA-99a, and lncRNA H19 was screened to predict the functional outcome at 3 months and the incidence of sICH after rtPA treatment. In the logistic regression analysis, the noncoding RNA score ≥ −0.336 (OR = 2.862 [1.029–7.958], p = 0.044) was an independent predictor of the poor outcome at 3 months after adjustment of clinical variables, the addition of the noncoding RNA score to the clinical model improved the discrimination (IDI% = 4.68 [0.65–8.71], p = 0.020), as well as the net reclassification (NRI% = 33.04 [0.54–71.49], p = 0.016). The noncoding RNA score ≥ −0.336 (OR = 5.250 [1.096–25.135], p = 0.038) was also independently predicted the sICH, the addition of the noncoding RNA score to the clinical variables improved discrimination and reclassification as well. The noncoding RNA score was also associated with the infarct volume and symptom improvement at 7 days after rtPA treatment. In conclusion, a higher neutrophilic noncoding RNA score provides predictive value to identify AIS patients with worse outcomes after rtPA treatment. miRNA-23a, miRNA-99a, and lncRNA H19 are worth further investigation for their effects in thrombolysis after AIS.

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Changes in Whole-Blood microRNA Profiles during the Onset and Treatment Process of Cerebral Infarction: A Human Study

Cited by 13 publications

References 28 publications

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

Effect of Butylphthalide combined with Oxiracetam on cognitive function, Intellectual recovery and serum inflammatory factors in patients with cognitive impairment after cerebral infarction

Neutrophilic noncoding RNAs predict outcomes of acute ischemic stroke patients treated with recombinant tissue plasminogen activator

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