Non-coding RNAs in acute ischemic stroke: from brain to periphery.

Acute ischemic stroke is a clinical emergency and a condition with high morbidity, mortality, and disability. Accurate predictive, diagnostic, and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined. With innovations in high-throughput gene sequencing analysis, many aberrantly expressed non-coding RNAs (ncRNAs) in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models. Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes, leading to neuroprotection or deterioration, thus ncRNAs can serve as therapeutic targets in acute ischemic stroke. Moreover, distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. In particular, ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke. In this review, we consolidate the latest progress of research into the roles of ncRNAs (microRNAs, long ncRNAs, and circular RNAs) in the pathological processes of acute ischemic stroke-induced brain damage, as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Teacher-Assessed Linguistic and Social Abilities in Chinese Children's Reading Acquisition: A Longitudinal Study.

The study explored the relationship between teacher assessments of students' general language-cognitive and social-emotional abilities and Chinese children's reading development over an academic year. A series of reading measures (including reading vocabulary, reading comprehension, and lexical inferencing ability) were administered to Chinese-speaking second graders (N = 123) across time. Meanwhile, their six head teachers and assistant head teachers were asked to complete assessments of their language-cognitive and social-emotional abilities prior to the first data collection. By utilizing multivariate analyses, the results demonstrated that teacher-assessed linguistic and social abilities contributed to children's reading abilities within and across time after autoregressive effects were controlled for. More specifically, language and cognitive abilities made a more salient contribution to reading performance over time. The study suggests that teacher assessments could have diagnostic and preventive functions for enhancing sustainable reading development among Chinese elementary-age students.

The Relationship Between Neuron-Specific Enolase and Clinical Outcomes in Patients Undergoing Mechanical Thrombectomy.

Purpose: Neuron-specific enolase (NSE) is considered a biomarker for the severity of nervous system diseases. We sought to explore whether serum NSE concentration in ischemic stroke patients undergoing mechanical thrombectomy (MT) is related to 3-month functional outcome and symptomatic intracranial hemorrhage (sICH). Patients and Methods: We retrospectively collected the data of acute ischemic stroke patients with anterior circulation infarction receiving MT within 6 h in our stroke center. Favorable outcome and poor outcome at 3 months were defined as modified Rankin Scale (mRS) score 0-2 and 3-6, respectively. sICH was defined according to the Heidelberg bleeding classification. We used multivariate logistic regression model and receiver operating characteristic curves to investigate the correlation between NSE and clinical outcomes. Results: Among the 426 patients enrolled, 40 (9.4%) patients developed sICH. Three-month favorable outcome in 160 (37.6%) and poor outcome in 266 (62.4%) patients were observed. Serum NSE levels was significantly correlated with 3-month mRS score (R = 0.473, P < 0.001). A cutoff value of 15.29 and 23.12 ng/mL for serum NSE was detected in discriminating 3-month poor outcome (area under the curve, 0.724) and sICH (area under the curve, 0.716), respectively. Multivariate analysis showed that high serum NSE levels were independently associated with 3-month poor outcome (odds ratio [OR] 5.049, 95% confidence interval [CI] 2.933-8.689, P<0.001) and sICH (OR 5.111, 95% CI 2.210-11.820, P < 0.001). Conclusion: Our study demonstrated that high serum NSE levels after receiving MT were independently associated with 3-month poor outcome and sICH in acute ischemic stroke patients. Serum NSE levels could be a good predictor of clinical outcomes for patients receiving MT.

A Novel Metabolic Score for Insulin Resistance and Symptomatic Intracranial Hemorrhage in Ischemic Stroke Patients After Endovascular Thrombectomy.

Background and Purpose: Insulin resistance plays a pivotal role in the pathophysiology of ischemic stroke. This study aimed to determine the relationship between the novel metabolic score for insulin resistance (METS-IR) and symptomatic intracranial hemorrhage (sICH) after endovascular thrombectomy (EVT) in stroke patients. Methods: We retrospectively included patients with large artery occlusion in the anterior circulation and treated by EVT from 2 stroke centers (Nanjing First Hospital from September 2019 to April 2022, and Jinling Hospital from September 2019 to July 2021). The METS-IR was used as an alternative marker of insulin resistance and calculated using laboratory data after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. Results: Of the 410 enrolled patients (mean age, 69.8 ± 11.7 years; 60.7% men), 50 (12.2%) were diagnosed as sICH. After adjusting for demographic characteristics, poor collateral status, and other potential confounders, higher METS-IR was revealed to be independently associated with sICH (odds ratio, 1.076; 95% confidence interval, 1.034-1.120; P = 0.001). Similar significant results were obtained when defining METS-IR as a categorical variable. The restricted cubic spline uncovered a linear relationship between METS-IR and sICH (P < 0.001 for linearity). Furthermore, adding METS-IR to the conventional model significantly improved the risk prediction for sICH (net reclassification improvement = 15.8%, P = 0.035; integrated discrimination index = 2.6%; P = 0.017). Conclusion: This study demonstrated a significant association between METS-IR score and sICH in ischemic stroke patients treated with EVT. It could help monitor and manage sICH in patients after EVT.

AVE 0991 Suppresses Astrocyte-Mediated Neuroinflammation of Alzheimer's Disease by Enhancing Autophagy.

Purpose: Our previous study has shown that AVE 0991, a nonpeptide analogue of Ang-(1-7), ameliorates cognitive decline and inhibits NLRP3 inflammasome of astrocytes in Alzheimer's disease model mice. Additionally, several studies have suggested that activation of autophagy appears to effectively inhibit the progression of neuroinflammation. However, it is unclear whether AVE 0991 can modulate astrocyte autophagy to suppress neuroinflammation in Alzheimer's disease. Materials and Methods: APP/PS1 mice and Aß-treated primary astrocytes were used as the research objects in vivo and in vitro, respectively. Water maze test was used to evaluate cognitive function of mice, Nissl staining and immunofluorescence staining was used to assess neuronal damage. ELISA kits were used to detect the levels of Ang-(1-7) and Aß in the cortex, and qRT-PCR was used to detect the expression of cortical inflammation-related mediators. The expression of autophagy-related proteins in cortex were detected by Western blot. The upstream molecular responses involved in inflammation inhibition by AVE 0991 were validated by means of using the Mas1 antagonist and autophagy inhibitor. Results: We found that 30 days of intraperitoneal administration of AVE 0991 improved. Aß deposition, neuronal death, and cognitive deficits in APP/PS1 Alzheimer's disease model mice. Moreover, AVE 0991 treatment greatly suppressed astrocyte-mediated inflammation and up-regulated the expression of autophagy. Furthermore, the inhibitory effect of AVE 0991 on the expression of inflammatory factors was reversed by 3-MA, an autophagy inhibitor. Conclusion: These findings suggest that regulation of autophagy is critical for inhibiting astrocyte neuroinflammatory responses and demonstrate a potential neuroprotective mechanism by which AVE 0991 could suppress neuroinflammatory responses by enhancing autophagy.

Construction of a Glycaemia-Based Signature for Predicting Acute Kidney Injury in Ischaemic Stroke Patients after Endovascular Treatment.

Background: Hyperglycaemia is thought to be connected to worse functional outcomes after ischaemic stroke. However, the association between hyperglycaemia and acute kidney injury (AKI) after endovascular treatment (EVT) remains elusive. The purpose of this study was to investigate the influence of glycaemic on AKI after EVT. Methods: We retrospectively collected the clinical information of patients who underwent EVT from April 2015 to August 2021. Blood glucose after EVT was recorded as acute glycaemia. Chronic glucose levels were estimated by glycosylated haemoglobin (HbA1c) using the following formula: chronic glucose levels (mg/dL) = 28.7 × HbA1c (%) − 46.7. AKI was defined as an increase in maximum serum creatinine to ≥1.5 baseline. We evaluated the association of AKI with blood glucose. A nomogram was established to predict the risk of AKI, and its diagnostic efficiency was determined by decision curve analysis. Results: We enrolled 717 acute ischaemic stroke patients who underwent EVT. Of them, 205 (28.6%) experienced AKI. Acute glycaemia (OR: 1.007, 95% CI: 1.003−1.011, p < 0.001), the acute/chronic glycaemic ratio (OR: 4.455, 95% CI: 2.237−8.871, p < 0.001) and the difference between acute and chronic glycaemia (ΔA-C) (OR: 1.008, 95% CI: 1.004−1.013, p < 0.001) were associated with the incidence of AKI. Additionally, age, atrial fibrillation, ASITN/SIR collateral grading, postoperative mTICI scale, and admission NIHSS were also significantly correlated with AKI. We then created a glycaemia-based nomogram, and its concordance index was 0.743. The net benefit of the nomogram was further confirmed by decision curve analysis. Conclusions: The glycaemia-based nomogram may be used to predict AKI in ischaemic stroke patients receiving EVT.

Dual Antiplatelet Therapy in Patients With Minor Stroke Receiving Intravenous Thrombolysis.

INTRODUCTION: Concern over the potential severe bleeding risk of dual antiplatelet therapy for patients with minor stroke after intravenous thrombolysis (IVT) leads to different antiplatelet strategies in the secondary prevention of stroke. Our aim was to investigate the effect of dual antiplatelet therapy on patients with minor ischemic stroke receiving IVT. METHODS: From November 2016 to April 2021, a total of 855 consecutive patients who received IVT were observed. We collected and analyzed demographic characteristics, medical history, clinical information, and important time metrics of patients with minor ischemic stroke. Comparative and multivariate logistic regression analyses were used to explore the clinical significance of single or dual antiplatelet therapy after IVT. Propensity score matching analyses (1:1 matching including baseline characteristics of patients) were also performed. RESULTS: A total of 245 patients were enrolled in the study (118 patients in the single antiplatelet therapy group and 127 patients in the dual antiplatelet group). No significant difference was found in baseline characteristics except stroke etiology (p < 0.001) for patients with minor stroke. The dual antiplatelet group showed a higher proportion of 90-day modified Rankin Scale (mRS) (0-1) than the single antiplatelet group (p = 0.030). Furthermore, patients receiving dual antiplatelet therapy had excellent outcomes (90-day mRS 0-1) after adjustment (odds ratio [OR] 2.76, 95% CI 1.27-6.01, p = 0.010). Other secondary outcomes (recurrent stroke within 90 days, symptomatic intracerebral hemorrhage, and early neurological deterioration) were not significantly different between the two groups. These findings were generally consistent in propensity score analyses. CONCLUSIONS: Dual antiplatelet therapy may be a potential therapeutic approach in patients with minor stroke receiving IVT. Further randomized controlled trials are required to confirm this finding.

SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression.

BACKGROUND: Abnormal expression of long noncoding RNAs (lncRNAs) has been reported in the acute stage of acute ischemic stroke (AIS). This study aimed to explore differential lncRNA expression in the subpopulations of peripheral blood mononuclear cells (PBMCs) from AIS patients and further evaluate its underlying mechanisms in stroke-induced immunosuppression. METHODS: We reanalyzed lncRNA microarray data and investigated abnormally expressed lncRNAs in the subpopulations of PBMCs by magnetic cell sorting and real-time quantitative PCR. The potential mechanism of small nucleolar RNA host gene 15 (SNHG15) was explored through in vitro and in vivo approaches. RESULTS: The stroke-induced SNHG15 acted as a checkpoint to inhibit peripheral inflammatory responses. Functional studies showed that SNHG15 promoted M2 macrophage polarization. Mechanistically, SNHG15 expression was dysregulated through the Janus kinase (JAK)-signal transducer and activator of transcription 6 (STAT6) signaling pathway. SNHG15, localized in the cytoplasm, interfered with K63-linked ubiquitination of tumor necrosis factor receptor-associated factor 2 and thereby repressed the activation of mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways and prevented the production of proinflammatory cytokines. Administration of an adenovirus targeting SNHG15 improved stroke-induced immunosuppression in mice. CONCLUSIONS: This study identified SNHG15 as a negative regulator of inflammation in stroke-induced immunosuppression, suggesting it as a novel biomarker and therapeutic target in stroke-associated infection. Trial registration ClinicalTrials.gov NCT04175691. Registered November 25, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691 .

Cumulative experience improves the procedures of mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy has been widely performed for large vessel occlusion stroke. The present study aimed to determine whether cumulative experience could improve thrombectomy outcomes. METHODS: In this retrospective single-center analysis, patients who underwent mechanical thrombectomy with the Solitaire stent in 3 years from 25 April 2015 were enrolled in the current study. Patients' characteristics, durations of admission and treatment, recanalization rates, clinical outcomes, and hemorrhage transformation rates were compared among the 3 years. Logistic analysis was used to analyze the independent correlation of the years and procedural outcomes. RESULTS: A total of 222 patients underwent mechanical thrombectomy in the 3 years: 50 in the first year, 68 in the second year, and 104 in the third year. Door-to-puncture time (P < 0.001) and puncture-to-recanalization time (P = 0.033) decreased significantly among the 3 years, while successful recanalization rates increased (P = 0.001). Logistic regression analysis showed an independent increase in the successful recanalization rates in the second year and third year (P = 0.020, P = 0.001) as compared to that in the first year. CONCLUSIONS: Cumulative experience might improve the procedures of mechanical thrombectomy. The current findings suggested a potential benefit for centralization in the treatment of large vessel occlusion stroke.

Clinical significance of stroke nurse in patients with acute ischemic stroke receiving intravenous thrombolysis.

BACKGROUND: Reports have proven that shorter door-to-needle time (DTN time) indicates better outcomes in AIS patients received intravenous thrombolysis. Efforts have been made by hospitals and centers to minimize DTN time in many ways including introducing a stroke nurse. However, there are few studies to discuss the specific effect of stroke nurse on patients' prognosis. This study aimed to compare consecutive AIS patients before and after the intervention to analyze the effect of stroke nurse on clinical outcome of AIS patients. METHODS: In this retrospective study, we observed 1003 patients from November 2016 to December 2020 dividing in two groups, collected and analyzed AIS patients' medical history, clinical assessment information, important timelines, 90 mRS score, etc. Comparative analysis and mediation analysis were also used in this study. RESULTS: A total of 418 patients was included in this study, and 199 patients were enrolled in the stroke nurse group and 219 was in the preintervention group. Baseline characteristics of patients showed no significant difference except there seems more patients with previous ischemic stroke history in the group of stroke nurse. (p = 0.008). The median DTN time significantly decreased in the stroke nurse group (25 min versus 36 min, p < 0.001) and multivariate logistic regression analysis showed the 90-day mRS clinical outcome significantly improved in the stroke nurse group (p = 0.001). Mediation analysis indicated the reduction of DTN time plays a partial role on the 90 days mRS score and the stroke nurse has some direct effect on the improvement of clinical outcome (p = 0.006). CONCLUSIONS: The introduction of stroke nurse is beneficial to clinical outcome of AIS patients and can be use of reference in other hospitals or centers.