In acute ischemic stroke therapy, potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species (ROS) during ischemic reperfusion. Herein, a novel 2D neuroprotective agent (AFGd-LDH) is reported, comprising Gd-containing layered double hydroxide nanosheets (Gd-LDH, as a drug nanocarrier/MRI contrast agent), atorvastatin (ATO, as a neuroprotective drug) and the ferritin heavy subunit (FTH, as a blood brain barrier transport agent). Experiments revealed AFGd-LDH to possess outstanding antioxidant activity, neuroprotective properties, blood‒brain barrier transit properties, and biocompatibility. In vitro studies demonstrated the ROS scavenging efficiency of AFGd‒LDH to be ∼90%, surpassing CeO₂ (50%, a ROS scavenger) and edaravone (52%, a clinical neuroprotective drug). Ischemia‒reperfusion model studies in mice showed AFGd‒LDH could dramatically decrease apoptosis induced by reperfusion, reducing the infarct area by 67% and lowering the neurological deficit score from 3.2 to 0.9. AFGd-LDH also offered outstanding MRI performance, thus enabling simultaneous imaging and ischemia reperfusion therapy.

The C-Reactive Protein-Triglyceride-Glucose Index (CTI) has been proposed as a novel biomarker for insulin resistance and inflammation. However, research on the relationship between CTI changes and stroke is limited. This study aims to investigate the association between changes in CTI and stroke risk. Participants were drawn from the China Health and Retirement Longitudinal Study (CHARLS). Stroke was defined as self-reported stroke. K-means clustering analysis was used to classify CTI changes, and cumulative CTI (cuCTI) was calculated as follows: (CTI2012 + CTI2015)/2 × time. To assess the association between CTI and stroke risk, Cox regression and restricted cubic spline (RCS) regression models were applied. A total of 4,364 participants were included in the study, among whom 323 (7.4%) experienced a stroke. The risk of stroke increased with higher levels of cuCTI. In the multivariable-adjusted model, Cox regression analysis showed that, compared with the lowest quartile (Q1), participants in the highest quartile (Q4) had a significantly increased risk of stroke by 103% (HR = 1.90, 95% CI: 1.30–2.78, P < 0.001). Furthermore, stroke risk increased progressively across ascending cuCTI quartiles (P for trend < 0.001). RCS analysis demonstrated a linear association between cuCTI and stroke risk (for nonlinearity, p < 0.001). K-means clustering identified three distinct trajectories of CTI variation. Participants with moderate and elevated CTI levels (HR = 1.53, 95% CI: 1.17–2.00, P = 0.001) and those with high CTI levels showing a slow increasing trend (HR = 1.75, 95% CI: 1.25–2.48, P < 0.001) had a significantly higher risk of stroke. This study demonstrates that both cuCTI and CTI changes are associated with stroke risk in middle-aged and older adults, particularly for those with consistently high CTI levels, which are linked to a significantly increased stroke risk. Monitoring long-term CTI changes and maintaining relatively low levels may help prevent stroke in this population.

This study analyzed the rupture risk of intracranial aneurysms (IAs) according to aneurysm characteristics by comparing the differences between two aneurysms in different locations within the same patient. We utilized this self-controlled model to exclude potential interference from all demographic factors to study the risk factors related to IA rupture. A total of 103 patients were diagnosed with IAs between January 2011 and April 2015 and were enrolled in this study. All enrolled patients had two IAs. One IA (the case) was ruptured, and the other (the control) was unruptured. Aneurysm characteristics, including the presence of a daughter sac, the aneurysm neck, the parent artery diameter, the maximum aneurysm height, the maximum aneurysm width, the location, the aspect ratio (AR, maximum perpendicular height/average neck diameter), the size ratio (SR, maximum aneurysm height/average parent diameter) and the width/height ratio (WH ratio, maximum aneurysm width/maximum aneurysm height), were collected and analyzed to evaluate the rupture risks of the two IAs within each patient and to identify the independent risk factors associated with IA rupture. Multivariate, conditional, backward, stepwise logistic regression analysis was performed to identify the independent risk factors associated with IA rupture. The multivariate analysis identified the presence of a daughter sac (odds ratio [OR], 13.80; 95% confidence interval [CI], 1.65–115.87), a maximum aneurysm height ≥7 mm (OR, 4.80; 95% CI, 1.21–18.98), location on the posterior communicating artery (PCOM) or anterior communicating artery (ACOM; OR, 3.09; 95% CI, 1.34–7.11) and SR (OR, 2.13; 95% CI, 1.16–3.91) as factors that were significantly associated with IA rupture. The presence of a daughter sac, the maximum aneurysm height, PCOM or ACOM locations and SR (>1.5±0.7) of unruptured IAs were significantly associated with IA rupture.

Background and purpose: We aimed to investigate the effect of smoking on the risk of intracranial aneurysm (IA) rupture (IAR), specifically relationship between the number of cigarettes smoked per day (CPD) or smoking index and the risk of IAR. Methods: We performed a single-center case–control study of consecutive patients evaluated or treated for IA at our institution from June 2015 to July 2016. Cases were patients with a ruptured IA. Two age- and sex-matched controls with an unruptured IA were included per case. Conditional logistic regression models were used to assess the relationship between both the CPD and smoking index (CPD × years of smoking) and IAR. Results: The study population included 127 cases of IAR and 254 controls. The higher IAR risk was associated with cigarette smoking (both current and former) (OR, 2.3; 95% CI, 1.1–4.8; P = 0.029). Our subgroup analysis of smokers revealed a significant association between IAR risk and current smoking (OR, 2.8; 95% CI, 1.2–6.3; P = 0.012), current heavy smoking (CPD ≥ 20) (OR, 3.9; 95% CI, 1.4–11.0; P = 0.007), and a smoking index ≥800 (OR, 11.4; 95% CI, 2.3–24.5; P = 0.003). Former smoking was not significantly associated with IAR (OR, 1.1; 95% CI, 0.3–4.0; P = 0.929). Conclusion: A dose–response relationship has been noted for intensity and duration of smoking consumption and increased risk of IAR. As smoking is modifiable, this finding is important to managing patients with IAs to quit or reduce smoking prior to life-threatening subarachnoid hemorrhage.

Background: Subarachnoid hemorrhage (SAH) is a severe stroke subtype that lacks effective treatment. Exosomes derived from human dental pulp stem cells (DPSCs) are a promising acellular therapeutic strategy for neurological diseases. However, the therapeutic effects of DPSC-derived exosomes (DPSC-Exos) on SAH remain unknown. In this study, we investigated the therapeutic effects and mechanisms of action of DPSC-Exos in SAH. Materials and methods: SAH was established using 120 male Sprague-Dawley rats. One hour after SAH induction, DPSC-Exos were administered via tail vein injection. To investigate the effect of DPSC-Exos, SAH grading, short-term and long-term neurobehavioral assessments, brain water content, western blot (WB), immunofluorescence staining, Nissl staining, and HE staining were performed. The role of miR-197-3p/FOXO3 in regulating pyroptosis was demonstrated through miRNA sequencing, bioinformatics analysis, and rescue experiments. The SAH model in vitro was established by stimulating BV2 cells with hemoglobin (Hb) and the underlying mechanism of DPSC-Exos was investigated through WB and Hoechst/PI staining. Results: The expressions of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were increased after SAH. DPSC-Exos alleviated brain edema and neuroinflammation by inhibiting the expression of FOXO3 and reducing NLRP3 inflammasome activation, leading to improved neurobehavioral functions at 24 h after SAH. In vitro, the expression of the NLRP3 inflammasome components (NLRP3 and caspase1-p20), GSDMD-N, and IL-18 was inhibited in BV2 cells pretreated with DPSC-Exos. Importantly, DPSC-Exos overexpressing miR-197-3p had a more obvious protective effect than those from NC-transfected DPSCs, while those from DPSCs transfected with the miR-197-3p inhibitor had a weaker protective effect. Functional studies indicated that miR-197-3p bound to the 3ʹ-untranslated region of FOXO3, inhibiting its transcription. Furthermore, the overexpression of FOXO3 reversed the protective effects of miR-197-3p. Conclusions: DPSC-Exos inhibited activation of the NLRP3 inflammasome and related cytokine release via the miR-197-3p/FOXO3 pathway, alleviated neuroinflammation, and inhibited microglial pyroptosis. These findings suggest that using DPSC-Exos is a promising therapeutic strategy for SAH. Graphical

Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.