Current neurovascular research最新文献

Introduction: Early Brain Injury (EBI) significantly contributes to poor neurological outcomes and death following subarachnoid hemorrhage (SAH). The mechanisms underlying EBI post-SAH remain unclear. This study explores the relationship between serial cerebral blood flow (CBF) changes and neurological symptoms, as well as the mechanisms driving CBF changes in the ultra-early stages after experimental SAH in mice.

Methods: SAH was induced by endovascular perforation in male ddY mice. Mice were sacrificed at 6, 12, 24, and 48 h after behavioral tests using the modified neurological score and grid walking test, and CBF was measured via Laser Speckle Flow Imaging (LSFI). Neurofunctional evaluation, CBF analysis, and Western blotting were used to assess SAH-induced damage.

Results: Neurological symptoms were significantly worse at 12 h post-SAH compared to sham (9.5 ± 1.7 vs. 25.6 ± 0.63, respectively; p < 0.0001). CBF was significantly reduced at 12 h post- SAH compared to sham (35.34 ± 8.611 vs. 91.06 ± 12.45, respectively; p < 0.0001). Western blotting revealed significantly elevated thrombin and matrix metalloproteinase 9 levels 12 h post-SAH (p < 0.05).

Conclusion: Our results suggest that microthrombus formation peaked at 12 h post-SAH, potentially causing EBI and worsening neurological symptoms. Microthrombus formation in the ultraearly stages may represent a novel therapeutic target for managing EBI.

Introduction: Post-stroke dysphagia (PSD) is a common complication after acute stroke. It can be effectively alleviated by electroacupuncture (EA) stimulation at the Baihui acupoint; however, the underlying mechanism remains unclear.

Methods: Male ICR mice were used, and the suture occlusion method was employed to establish the middle cerebral artery occlusion (MCAO) mouse model. EA stimulation was applied to the Baihui acupoint for intervention. After treatment, the survival rate of the mice was assessed. Subsequently, a water swallow test was conducted to evaluate the degree of dysphagia in the mice. Additionally, neurological function was assessed through Garcia scoring and measurement of serum Ca²⁺-Mg²⁺-ATPase activity. Fur-thermore, MRI was utilized to evaluate the therapeutic effects of EA on cerebral infarction and edema rates. Then, the antioxidant activity of the EA intervention was assessed by measuring indicators of oxida-tive damage. Finally, the expressions of gamma- aminobutyric acid type B receptor subunit 1 (GAB-ABR1), N-methyl-D-aspartate receptor 1 (NMDAR1) were detected through WB, RT-qPCR, and immu-nofluorescence.

Results: EA intervention effectively increased the survival rate of MCAO mice and alleviated their dysphagia. Additionally, the impaired neurological function of the mice was improved, and cerebral infarction and edema rates were reduced. Furthermore, EA alleviated oxidative stress in mice, reduced damage to neurons in the nucleus ambiguus, and upregulated GABABR1 while downregulating NMDAR1.

Discussion: Although we suggested that EA may exert therapeutic activity for PSD by maintaining the balance of NMDAR1 and GABABR1, this conclusion still requires further experimental validation.

Conclusion: EA stimulation of the Baihui acupoint was effective in treating PSD, which was related to its ability to improve damaged neurons, upregulate GABABR1, and downregulate NMDAR1. These findings provided a new insight into the mechanisms of EA treatment for PSD and serve as a theoretical basis for future clinical research.

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.

Introduction: Although ischemic stroke is associated with complex changes in the autonomic nervous system, the circadian patterns of heart rate (HR) and heart rate variability (HRV) in wake-up stroke (WUS) remain poorly understood. This study compared 24-hour heart rate and HRV patterns between patients with and without WUS.

Methods: This retrospective observational case-control study involved 104 patients with acute ischemic stroke (9 WUS, 95 non-WUS). HRV analysis was performed using a 14-day continuous electrocardiography patch monitor. Time- and frequency-domain HRV metrics were calculated, and 24-hour differences were assessed using generalized additive mixed models (GAMMs), adjusting for confounders.

Results: WUS patients had significantly higher HRs (80.60 ± 12.49 vs. 73.22 ± 14.49 beats per minute, P < 0.001) and lower HRV-measured by SDNN (28.06 ± 21.68 vs. 39.70 ± 25.73 milliseconds, P < 0.001), RMSSD (15.78 ± 12.49 vs. 22.16 ± 19.22 milliseconds, P < 0.001), and pNN50 (1.03% ± 2.78% vs. 2.61% ± 5.15%, P < 0.001)-than non-WUS patients. GAMMs indicated that patients with WUS experienced significant autonomic dysregulation, characterized by higher HRs, lower HRV, and altered circadian rhythms compared to those with non-WUS. These differences were particularly evident during the early morning hours.

Discussion: WUS patients exhibited distinct 24-hour HR and HRV profiles, characterized by higher HRs and reduced autonomic variability compared to non-WUS patients. These differences align with patterns typically associated with lower parasympathetic activity rather than elevated sympathetic tone.

Conclusion: WUS is associated with impaired autonomic regulation and disrupted circadian patterns of HR and HRV.

Stroke is associated with a high rate of long-term disability, with motor and sensory impairments of the limbs being among the most common sequelae. Conventional treatments often show limited effectiveness in fully restoring function and may lead to persistent or irreversible deficits over time. Extracorporeal shock wave therapy (ESWT), a non-invasive therapeutic modality, has emerged as a potentially effective intervention for improving motor function after stroke. Its primary therapeutic actions include enhancing blood and lymphatic circulation in the affected limbs, promoting cellular repair, relieving pain, increasing joint range of motion, reducing pathological muscle spasms, strengthening connective tissue, and mitigating abnormal tissue calcification. Given these effects, ESWT may provide direct therapeutic benefits for patients with post-stroke limb dysfunction, with reported outcomes such as pain reduction, increased pain threshold, improved sensory function, decreased abnormal muscle tone, and enhanced overall motor ability. Therefore, this article reviews current research on ESWT for post-stroke motor dysfunction, aiming to explore its therapeutic mechanisms and provide evidence-based insights to support motor function rehabilitation after stroke.

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.