Background: It is unclear whether miR-491-5p, miR-206, miR-21-5p or miR-3123 are associated with functional outcomes and hemorrhagic transformation (HT) after acute ischemic stroke (AIS). In this study, we aimed to investigate the correlation between these four microRNAs and functional outcomes, as well as spontaneous HT after AIS; Methods: We included 215 AIS patients and retrospectively assayed for miR-21-5p, miR-206, miR-3123 and miR-491-5p levels in serum. Poor functional outcome was defined as a modified Rankin Scale score ≥ 3. Spontaneous HT referred to hemorrhage detected in follow-up brain imaging but not on admission, without reperfusion therapies. Logistic regression, generalized additive model and 2-piecewise regression model were used to explore the independent, non-linear correlation between miRNA expression levels and outcomes; Results: We included 215 AIS patients. Higher miR-491-5p level independently reduced the risk of poor functional outcomes at 1 year (OR 0.90, 95% CI 0.82–0.98, corrected p value = 0.044). Higher miR-206 level significantly increased the risk of spontaneous HT (OR 1.64, 95% CI 1.17–2.30, corrected p value = 0.016). There was a nonlinear correlation found between miR-491-5p level and 1 year outcome with an inflection point of 2.180, while an approximately linear correlation was observed with an inflection point of 2.037 between miR-206 level and spontaneous HT; Conclusions: Higher serum miR-491-5p level independently reduced risk of 1-year poor functional outcome of AIS patients. Higher serum miR-206 level independently increased the risk of spontaneous HT in AIS patients. These two miRNAs may be as the potential biomarkers for improving prognosis after AIS.

Introduction: Large hemispheric infarction (LHI) can lead to fatal complications such as malignant brain edema (MBE). We aimed to investigate the correlation between heart-rate-to-blood-pressure ratios and MBE or one-month death after LHI. Methods: We prospectively included LHI patients from a registered cohort. Hourly heart-rate-to-blood-pressure ratios were recorded as a variation of the traditional shock index (SI), SI_s and SI_d (systolic and diastolic pressures, respectively), and calculated for mean and variability (standard deviation) in 24 h and two 12 h epochs (1–12 h and 13–24 h) after onset of symptoms. MBE was defined as neurological deterioration symptoms with imaging evidence of brain swelling. We employed a generalized estimating equation to compare the trend in longitudinal collected SI_s and SI_d between patients with and without MBE. We used multivariate logistic regression to investigate the correlation between SI_s, SI_d and outcomes. Results: Of the included 162 LHI patients, 28.4% (46/162) developed MBE and 25.3% (40/158) died within one month. SI_s and SI_d increased over baseline in all patients, with a similar ascending profile during the first 12 h epoch and a more intensive increase in the MBE group during the second 12 h epoch (p < 0.05). During the overall 24 h, patients with greater SI_d variability had a significantly increased MBE risk after adjustment (OR 3.72, 95%CI 1.38–10.04). Additionally, during the second 12 h epoch (13–24 h after symptom onset), patients developing MBE had a significantly higher SI_d level (OR 1.18, 95%CI 1.00–1.39) and greater SI_d variability (OR 3.16, 95%CI 1.35–7.40). Higher SI_d and greater SI_d variability within 24 h independently correlated with one-month death (all p < 0.05). Within the second 12 h epoch, higher SI_s, higher SI_d and greater SI_d variability independently correlated with one-month death (all p < 0.05). No significant correlation was observed in the first 12 h epoch. Conclusions: Higher and more fluctuated heart-rate-to-blood-pressure ratios independently correlated with MBE development and one-month death in LHI patients, especially during the second 12 h (13–24 h) epoch after onset.

Introduction: Previous preclinical studies reported that the level of serum EphrinA1 was associated with blood-brain barrier disruption; however, its role in predicting parenchymal hematoma (PH) after ischemic stroke is underexplored. We aimed to explore the association between the level of serum EphrinA1 and PH in patients with ischemic stroke. Methods: Patients with ischemic stroke after onset from West China Hospital, Sichuan University, were prospectively enrolled between January 2017 and December 2019. The level of serum EphrinA1 at baseline was measured after admission. PH was diagnosed as hematoma within the infarct territory detected on the brain CT/MRI scans within 7 days after onset but not on the initial scan according to European Cooperative Acute Stroke Study (ECASS) III criteria. The association between the level of serum EphrinA1 and PH after ischemic stroke was assessed by multiple logistic regression analysis. Results: A total of 667 patients were included in the final analysis. The mean age was 67.20 ± 14.31 years, and 57.87% (368/667) were males. Of the 667 patients, 65 (9.75%) patients had PH. The median of EphrinA1 on admission was 82.83 ng/mL (IQR, 70.11–93.75 ng/mL). Compared with patients without PH, those with PH had a higher level of serum EphrinA1 (p = 0.024). Patients were divided into 3 categories based on EphrinA1 tertiles (T1, 93.75 ng/mL, n = 222). After adjusting for age, sex, atrial fibrillation, smoking, statins, antiplatelets, Trail of Org 10172 in Acute Stroke Treatment (TOAST) classification and National Institutes of Health Stroke Scale (NIHSS) score ≥15, patients in the second and third EphrinA1 tertiles showed a significant increase in PH compared with those in the lowest tertile (OR 2.44, 95% CI: 1.10–5.40, p = 0.028; OR 2.61, 95% CI: 1.19–5.74, p = 0.017, respectively). Additionally, adjusting for reperfusion therapy (thrombolysis and/or endovascular therapy), only patients in the highest group (tertile 3) had a significantly higher risk of PH compared to the lowest group (OR 2.30, 95% CI: 1.03–5.13, p = 0.042). Conclusion: Higher serum EphrinA1 is independently associated with a higher risk of PH after ischemic stroke. Future studies with larger sample sizes are needed to validate our findings and elucidate the potential role of EphrinA1 in PH.