Current neurovascular research最新文献

Introduction: High On-Treatment Platelet Reactivity (HTPR) is frequently observed after carotid endarterectomy (CEA) or stenting (CAS), but its association with adverse events remains uncertain. This systematic review and meta-analysis evaluate the association between HTPR and recurrent vascular events in these patients.

Methods: EMBASE, PubMed, and Cochrane Library were searched for eligible studies from inception to July 1, 2024. Two independent reviewers screened the records, extracted data, and assessed the bias using predefined criteria. A meta-analysis was conducted using RevMan 5.4 software. The primary outcome was the risk of recurrent ischemic events in patients with HTPR. Secondary outcomes included the risk of hemorrhage and carotid restenosis.

Results: Eight studies involving 1,052 patients were included in the meta-analysis. This metaanalysis found that HTPR significantly increased the risk of adverse vascular events (OR = 2.41, 95% CI: 1.37-4.24), particularly in CAS patients (OR = 1.85, 95% CI: 1.14-2.98), but not in CEA patients (OR = 4.53, 95% CI: 0.52-39.12). Furthermore, HTPR was not significantly associated with an increased risk of bleeding (OR = 0.90, 95% CI: 0.24-3.37) or carotid restenosis (OR = 1.70, 95% CI: 0.38-7.55).

Discussion: This meta-analysis demonstrates that HTPR may increase the risk of recurrent ischemic events in CAS patients, supporting the clinical utility of platelet function monitoring in this population. However, no significant association was observed between HTPR and hemorrhage or restenosis. These findings should be interpreted cautiously due to study limitations, including small sample sizes and heterogeneity in platelet function assessment methodologies. Large-scale prospective studies with standardized protocols are warranted to validate these observations.

Conclusion: HTPR may be associated with an increased risk of recurrent ischemic events in patients undergoing CAS, highlighting the potential value of platelet function monitoring.

Aim: The aim of this study was to explore etiologies and risk factors by age and sex in young adult patients with ischemic stroke.

Methods: We recruited patients with ischemic stroke aged between 18 and 49 years. We assessed pathological etiologies by the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification and risk factors by the International Pediatric Stroke Study (IPSS) classification. We explored the distribution of etiologies and risk factors by age and sex and investigated baseline features associated with functional outcomes at 3 months.

Results: Of 8521 stroke patients consecutively admitted, 1017 patients (11.9%) aged between 18-49 years, of whom large artery atherosclerosis was the most common etiology (n=375, 36.9%), followed by other determined cause (n=194, 19.1%) and undetermined cause (n=184, 18.1%). Compared to male patients, female patients had more cardioembolism (16.34% vs 8.42%) and less small artery occlusion (8.56% vs 17.76%). As age increased, the proportions of large artery atherosclerosis (P <0.001) and small artery occlusion (P <0.001) increased, and the proportion of other determined causes decreased (P <0.001). Of 184 patients with undetermined causes, 173 (94.0%) had at least one IPSS risk factor. A higher serum level of D-dimer at baseline was associated with an increased risk of unfavorable outcome (OR 1.118, 95% CI 1.052- 1.189), adjusting for the effect of age and stroke severity.

Conclusion: Approximately one-fifth of young patients with ischemic stroke had undetermined etiology, for whom the IPSS classification helps to explore risk factors. A higher level of Ddimer was associated with a higher risk of unfavorable outcomes at 3 months.

Objective: Regenerative therapy using stem cells to treat cerebral infarction is currently in the research phase. However, this method is costly. It also faces other significant challenges, including optimization of timing, delivery methods, and dosage. Therefore, more practical and effective therapies are required. Bioabsorbable artificial dura mater made from nonwoven Polyglycolic Acid (PGA) fabric is used clinically to treat cerebral infarction. Basic Fibroblast Growth Factor (bFGF) has attracted considerable attention as a potential therapeutic candidate for the treatment of cerebral infarctions. In this study, we aimed to prepare a bFGF-releasing PGA dura mater and investigate its therapeutic efficacy for the recovery of neurological function in a mouse model of focal cerebral infarction.

Methods: An artificial dura mater (Durawave) made from nonwoven PGA fabric was subjected to oxygen plasma treatment, followed by bFGF adsorption. The release of bFGF from the resulting PGA dura mater was evaluated in vitro using enzyme-linked immunosorbent assays. bFGF-releasing PGA dura mater was placed at the site of induced cerebral infarctions in mice. Neurological function was assessed 14 days after insertion, followed by a histological assessment.

Results: The prepared PGA dura mater released bFGF in a dose-dependent manner. Neurological function in the bFGF-treated groups was significantly better than that in the control group. bFGFreleasing PGA dura mater also significantly increased the number of neural progenitor cells in the peri-infarct cortex and striatum and showed a trend toward promoting angiogenesis.

Conclusion: bFGF-releasing PGA dura mater improved neurological function in a mouse model of focal cerebral infarction.

Objective: We aimed to investigate the prognostic factors associated with lobar intracerebral hemorrhage (ICH) and to construct convenient models to predict 3-month unfavorable functional outcomes or all-cause death.

Methods: Our study included 322 patients with spontaneous lobar ICH from 13 hospitals in Beijing as a derivation cohort. The clinical outcomes were unfavorable functional prognosis, defined as a modified Rankin Scale (mRS) score of 4-6, or all-cause death. Variable selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and two nomogram models were constructed. Additionally, multivariable logistic regression analysis was conducted to identify the factors associated with unfavorable prognosis. Finally, the Area Under The Receiver Operating Characteristic Curve (AUROC), calibration curve, and decision curve analyses (DCA) were performed to evaluate the models in both the derivation and external validation cohorts.

Results: Predictive factors for unfavorable functional outcomes in lobar ICH included age, dyslipidemia, ICH volume, NIHSS score, Stroke-Associated Pneumonia (SAP), and lipidlowering therapy. The model included age, GCS score, NIHSS score, antihypertensive therapy, in-hospital rehabilitation training, and ICH volume to predict all-cause mortality. Our models exhibited good discriminative ability, with an AUC of 0.897 (95% CI: 0.862-0.933) for unfavorable functional outcomes and 0.894 (95% CI: 0.870-0.918) for death. DCA and calibration curves confirmed the models' excellent clinical decision-making and calibration capabilities.

Conclusion: Nomogram models for predicting 3-month unfavorable outcomes or death in patients with lobar ICH were developed and independently validated in this study, providing valuable prognostic information for clinical decision-making.

Introduction: Stroke is a leading cause of death and disability globally, influenced by genetic, environmental, and metabolic factors. Although cerebrospinal fluid (CSF) metabolites are closely linked to stroke, their causal roles remain unclear.

Methods: We integrated genome-wide association study (GWAS) data on 338 CSF metabolites with stroke outcomes. Two-sample and reverse Mendelian randomization (MR) analyses were conducted to assess causal associations between metabolites and stroke, including its subtypes: ischemic stroke, cardioembolic stroke, large artery stroke, and small vessel stroke. Seven complementary MR methods, including inverse variance weighted (IVW), were applied to evaluate pleiotropy and heterogeneity, ensuring robust causal inference.

Results: Eighteen CSF metabolites showed significant associations with overall stroke, including six risk factors (e.g., creatinine; OR = 1.390, 95% CI: 1.167-1.656) and twelve protective factors (e.g., β-citrylglutamate; OR = 0.899, 95% CI: 0.827-0.977). Subtype analyses identified 14 metabolites linked to ischemic stroke, 31 to cardioembolic stroke, 6 to large artery stroke, and 19 to small vessel stroke. Reverse MR revealed that stroke causally influenced 9 metabolites, such as increased N-acetyltaurine (OR = 1.105) and decreased succinimide (OR = 0.814). Sensitivity analyses confirmed the robustness of these findings.

Discussion: Our study provides evidence that specific CSF metabolites play causal roles in different stroke subtypes and that stroke itself can alter CSF metabolic profiles, suggesting bidirectional interactions.

Conclusion: This work reveals novel mechanistic insights and identifies potential biomarkers and therapeutic targets for stroke diagnosis and precision medicine.

Background: Plasma osteoprotegerin (OPG) has been linked to poor prognosis following stroke, but its impact on post-stroke cognitive impairment (PSCI) is unknown. The purpose of our work was to analyze the relationship of OPG with PSCI.

Methods: Our study included 613 ischemic stroke subjects with plasma OPG levels. We used the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to assess PSCI. PSCI was defined as MMSE score <25 or MoCA score <23.

Results: As assessed by the MMSE score, the adjusted odds ratio for PSCI in the highest OPG tertile was 1.77, with a 95% confidence interval of 1.09 to 2.89 (P_trend=0.021), compared to that in the lowest tertile. We observed a positive linear relationship of plasma OPG levels with 3- month PSCI (P for linearity=0.046). Incorporating plasma OPG into conventional risk factors enhanced PSCI risk reclassification (all P <0.05). Consistent results were discovered when PSCI was evaluated using the MoCA score.

Conclusion: High plasma OPG levels were related to an elevated risk of 3-month PSCI, indicating that OPG might be an effective biomarker for predicting PSCI.

Introduction: Current genetic research on the relationship between hypertension and vertigo is limited, and traditional observational studies cannot establish a causal relationship due to design limitations, particularly regarding whether hypertension acts as a causal risk factor for specific vertigo subtypes, such as benign paroxysmal positional vertigo (BPPV).

Methods: This study employed a two-sample MR approach to infer causal relationships via genome- wide association study (GWAS) data, thereby addressing the limitations of traditional observational studies. In addition to analyzing the link between total vertigo and hypertension, we examined three major types of vertigo: central vertigo, benign paroxysmal positional vertigo (BPPV), and other peripheral vertigo. The study included 3834 cases of BPPV, 186 cases of central vertigo, 1293 cases of other peripheral vertigo, and 209,582 controls. Various MR methods, including the inverse variance weighted (IVW) approach, MR-Egger, weighted median, and simple mode, were employed to deduce the potential causative associations.

Results: A set of 53 genome-wide significant single-nucleotide polymorphisms (SNPs) associated with hypertension was identified as instrumental variables for subsequent MR analysis. The results indicated a significantly positive correlation between hypertension and the risk of total vertigo (OR: 1.16, 95% CI: 1.08-1.25, p <0.05), BPPV (OR: 1.12, CI: 1.01-1.24, and p =0.03), and other peripheral vertigo (OR: 1.19, 95% CI: 1.00-1.41, p =0.046), whereas no significant association was found with central vertigo (OR: 1.15, 95% CI: 0.74-1.80, p =0.53).

Discussion: This study provides genetic evidence for a positive association between hypertension and vertigo, particularly BPPV and peripheral vertigo, but not central vertigo. Hypertension may induce vestibular dysfunction via vascular changes leading to tissue hypoxia and cochlearvestibular degeneration. Limitations include small sample sizes for certain vertigo subtypes (e.g., central vertigo) and limited generalizability to non-European populations.

Conclusion: This MR analysis provides evidence supporting a potential causal relationship between hypertension and an increased risk of certain types of vertigo. These findings contribute to the understanding of risk factors and the early prediction of vertigo.

The PI3K/AKT and Nrf2 signaling systems are essential for neurogenesis, synaptic plasticity, and cellular survival, and their dysregulation has been linked to the progression of Alzheimer's disease (AD). Due to its complex pathophysiology, currently approved therapeutic agents only provide symptomatic relief and are often associated with serious side effects. Researchers have increasingly focused on natural bioactive compounds as potential therapies, with flavonoids emerging as promising candidates due to their diverse neuroprotective properties. These polyphenolic compounds exhibit notable anti-inflammatory, anti-apoptotic, and antioxidant effects, making them attractive therapeutic agents against AD. A key mechanism by which flavonoids exert neuroprotection is through modulation of the PI3K/AKT and Nrf2 signaling pathways. By enhancing neuronal resilience, reducing oxidative stress, inhibiting apoptosis, and regulating autophagy, flavonoids can mitigate neurodegenerative processes associated with AD. Additionally, they attenuate Aβ accumulation and tau hyperphosphorylation, both of which contribute to neuronal dysfunction, via PI3K/AKT activation and Nrf2 pathway regulation. In preclinical AD models, numerous flavonoids-including epicatechin, kaempferol, quercetin, and luteolin- have demonstrated neuroprotective effects through regulation of the PI3K/AKT and Nrf2 pathways. Despite these encouraging findings, further research is needed to determine optimal dosages, strategies for enhancing bioavailability, and the long-term effects of flavonoid-based therapies in AD. Future studies should focus on translating preclinical evidence into clinical trials, which could improve patient outcomes and quality of life. A deeper understanding of the molecular mechanisms underlying flavonoid activity, particularly their interaction with PI3K/AKT and Nrf2 pathways, may pave the way for novel neuroprotective therapies.