OBJECTIVE Intracerebral hemorrhage (ICH) induces severe secondary brain injury, in which microglial polarization plays a critical role in the progression of neuroinflammation. This study aimed to investigate the role of the E3 ubiquitin ligase NEDD4 in regulating microglial polarization and neuroinflammation following ICH, as well as the underlying molecular mechanisms. METHODS Hemin-treated BV2 microglia and an autologous whole-blood injection-induced ICH rat model using male Sprague-Dawley rats were established. Microglial polarization markers were evaluated by quantitative reverse transcription PCR (qRT-PCR) and immunofluorescence staining. Histological injury was assessed using Nissl staining and hematoxylin and eosin (H&E) staining. The interaction between NEDD4 and SIRT2, as well as SIRT2 ubiquitination, was examined by co-immunoprecipitation and ubiquitination assays. RESULTS NEDD4 expression was markedly decreased in both hemin-treated BV2 microglia and perihematomal brain tissues from male ICH rat model . Upregulation of NEDD4 alleviated histological injury and promoted microglial polarization toward the anti-inflammatory M2-like phenotype in a male ICH rat model. Mechanistically, NEDD4 directly interacted with SIRT2 and promoted its ubiquitination and proteasomal degradation. Rescue experiments further demonstrated that SIRT2 overexpression abolished the promotive effect of NEDD4 on microglial M2-like polarization. CONCLUSION NEDD4 attenuated neuroinflammation and histological injury after ICH likely by facilitating SIRT2 ubiquitination and degradation, thereby promoting microglial polarization toward the protective M2-like phenotype. These findings identify the NEDD4/SIRT2 axis as a previously uncharacterized regulatory link in ICH-induced neuroinflammation, revealing an upstream regulatory mechanism of SIRT2 in ICH pathology.
Background and purpose We assessed whether preventive intravenous tirofiban reduces early neurological deterioration (END) in acute ischemic stroke without thrombolysis or thrombectomy, and how population, timing and comparator differences affect interpretation. Methods A focused evidence update included PubMed searching through October 13, 2026, screening of 520 records and citation checks. Randomized and observational evidence were separated. Risk ratios (RRs) were analyzed using restricted maximum-likelihood models, with fixed-effect, Hartung–Knapp, prediction-interval and influence analyses. Abstract-level evidence was evaluated separately where eligibility was uncertain. Results Two randomized trials (1,395 participants) yielded discordant END estimates: RR 0.50 (95% CI 0.32–0.77) and 0.91 (0.67–1.22). The exploratory pooled RR was 0.69 (0.38–1.24; I²=79.6%; τ²=0.143), with marked model dependence. Four trials contributed 2,017 observed 90-day modified Rankin Scale 0–1 outcomes: RR 1.12 (1.05–1.19); modified Hartung–Knapp CI 1.01–1.23 and prediction interval 0.98–1.28. Excluding ESCAPIST because of discrepant published counts widened the modified Hartung–Knapp interval to 0.96–1.27. Separately, the BRANT abstract reported RR 1.01 (0.90–1.13); target-population eligibility was unconfirmed. Treatment-by-time interactions and mediation of functional benefit through END prevention were not established. Conclusions Preventive END effects are trial-specific. The functional signal is sensitive to source and model assumptions and does not establish END-mediated benefit. Imaging-guided selection and incremental benefit over optimized oral therapy require direct randomized evaluation, with standardized neurological, functional and bleeding outcomes.
Background and purpose Current secondary prevention guidelines generally target low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L after ischemic stroke, but the prognostic relevance of an early level <1.4 mmol/L remains unclear. We examined associations of LDL-C measured within 15 days with 12-month recurrent ischemic stroke and 90-day functional outcomes in patients with moderate-to-severe acute ischemic stroke (AIS). Methods This retrospective day-15 landmark cohort included 1,800 adults with admission National Institutes of Health Stroke Scale scores of 6–20. All were alive and recurrence-free at day 15. The last fasting LDL-C within 15 days defined groups of <1.4, 1.4–1.8, or >1.8 mmol/L. Cox and Fine–Gray models assessed recurrence. A partial proportional odds model assessed the 90-day modified Rankin Scale (mRS). Results Recurrent ischemic stroke occurred in 213 patients (11.8%). Recurrence proportions were 6.7%, 9.9%, and 14.2% across groups (global P = 0.014). Compared with >1.8 mmol/L, <1.4 mmol/L was associated with a lower recurrence hazard (adjusted hazard ratio 0.49, 95% confidence interval 0.28–0.83). Among 1,677 patients with mRS data, the pairwise common odds ratio (OR) was 1.38 (1.04–1.83), while the overall three-group P value was 0.056. Further adjustment for treatment and measurement day yielded a common OR of 1.37 (0.97–1.93). The day-121 analysis showed no clear association with later recurrence. Conclusions Lower early LDL-C was associated with a lower subsequent recurrence hazard among patients meeting the day-15 landmark criteria. Functional findings remained exploratory.
AIM With population aging and improved cancer survival, this study aims to analyze the temporal trends and disparities in stroke-related mortality among cancer patients from 1999 to 2023. METHODS Mortality data included deaths with cancer as the underlying cause and stroke as a contributing cause, extracted from the CDC WONDER database. Crude and age-adjusted mortality rates (AAMRs) (≥ 25 years) were calculated for the overall population and subgroups. Joinpoint regression with the jump model was used to analyze trends, estimating the annual percentage change (APC) and average annual percentage change. RESULTS From 1999 to 2023, a total of 280,490 stroke-related deaths occurred among cancer patients in the United States. The overall AAMR declined slowly from 1999 to 2014 (APC: -2.53, 95% CI: -2.77 to -2.29), but gradually increased from 2014 to 2023 (APC: 3.08, 95% CI: 2.57 to 3.59). Most stroke-related deaths were classified as unspecified stroke. Across all cancer types, patients with leukemia had the highest proportion of stroke-related deaths (4.10%). Similar temporal trends were observed across sex, race, age group, census region, and urbanization subgroups. High-risk populations included males, Non-Hispanic Black individuals, rural residents, and older adults. The proportion of deaths occurring in medical facilities decreased gradually, while the proportion of deaths at decedents' homes showed an upward trend, with a prominent shift in 2020. CONCLUSION The long-term decline in stroke-related mortality among U.S. cancer patients reversed after 2014, with significant disparities across subgroups. This underscores the need to improve stroke management among cancer patients. Given the aggregated nature of CDC WONDER data and the use of ICD codes, this study was limited to a descriptive analysis; individual-level data and exploration of factors driving the observed trends were unavailable, and the results should be interpreted with caution.
Background Stroke increasingly affects working-age individuals. Returning to work (RTW) is a critical rehabilitation goal for these patients. This study investigated the proportion of young adults in Northwest China who did not return to work (NRTW) 12 months after an ischemic stroke and identified factors associated with NRTW. Methods We conducted a retrospective analysis of young patients (18-49 years) with ischemic stroke, admitted between January 2017 to August 2019, who had stable employment before onset. Data collected included demographics, lifestyle, comorbidities, stroke etiology classification, clinical features (including NIHSS score and specific functional impairments at admission) and medical interventions. RTW status was determined at the 12-month follow-up. Missing data were handled using multiple imputation by chained equations (20 imputed datasets). Univariable and multivariable logistic regressions were applied to identify factors associated with NRTW. Results Among 339 previously employed patients (median age 44; 284 [83.78%] males), 106 (31.3%) had not returned to work at 12 months. Multivariable analysis identified female (OR = 3.02, 95% CI 1.21–7.52, P = 0.017) and pre-stroke manual labor (OR = 4.66, 95% CI 2.50–8.66, P < 0.001) as significant demographic factors positively associated with NRTW. A higher NIHSS score at admission was associated with NRTW (NIHSS 5–9 vs. 0–4: OR = 3.12, 95% CI 1.46–6.69, P = 0.003; NIHSS ≥ 10 vs. 0–4: OR = 6.69, 95% CI 2.35–19.04, P < 0.001). Regarding specific impairments, aphasia was significantly associated with NRTW (OR = 3.67, 95% CI 1.32–10.20, P = 0.013), while motor dysfunction showed a marginal positive association (OR = 1.83, 95% CI 0.99–3.35, P = 0.052). Cardioembolic stroke showed significant association in the model including specific clinical features (OR = 4.12, 95% CI 1.36–12.46, P = 0.012, Model 2), a finding that requires confirmation in larger studies. Conclusion A proportion of young stroke survivors in Northwest China do not resume work at 12 months after stroke. Key factors associated with failure to RTW include female sex, pre-stroke manual labor, greater stroke severity (higher NIHSS), and the presence of aphasia. Motor dysfunction may also be an important factor in RTW. The association of stroke etiology with RTW may be influenced by neurological severity. These findings highlight the need for targeted interventions to improve RTW outcomes in this population.
