Current neurovascular research最新文献

Background: Ischemic stroke is a major cause of death and disability worldwide and results from inadequate cerebrovascular blood supply; mitochondrial dysfunction plays an essential role in its pathogenesis. DL-3-n-butylphthalide (NBP) is an effective medicine for ischemic stroke that reduces cell apoptosis and improves long-term prognosis.

Objective: Whether and how NBP regulates mitochondria-associated apoptosis in cerebral ischemia- reperfusion injury remains unclear.

Methods: Male Sprague Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) stroke and treated with low (20 mg/kg) or high (80 mg/kg) concentrations of NBP. The Omi/HtrA2 inhibitor UCF-101 was used as a positive control. Cerebral infarction, neuron injury and neuronal apoptosis were assessed to determine the efficacy of NBP compared to UCF-101. We assessed the expression of the Omi/HtrA2 signaling pathway by western blotting and tested the mRNA expression of mitochondrial metabolism-related genes by PCR.

Results: Compared to the MCAO group, both low and high concentrations of NBP substantially improved cerebral infarction, neuron injury, and neuronal apoptosis; high concentrations of NBP were more potent than low concentrations. The expression of proteins of the mitochondrial Omi/HtrA2 signaling pathway, including Omi/HtrA2, XIAP, PARL, OPA1, CHOP, and ClpP, was inhibited in the NBP group.

Conclusion: Overall, early application of NBP attenuated cerebral ischemia-reperfusion injury by inhibiting mitochondrial Omi/HtrA2-mediated apoptosis in rats. Our study supports a novel neuroprotective mechanism of NBP, making it a promising therapeutic agent for ischemic stroke.

Recurrent ischemic stroke (IS) is one of the leading causes of disability and death worldwide. Patients with recurrent IS, in comparison with survivors of the initial non-cardiogenic IS, have more serious neurological deficit and longer hospital stay with heavier family and socio-economic burden. Therefore, recurrent IS is a major challenge that we urgently need to address. The recurrence rate of non-cardiogenic IS is not zero and even shows an increasing trend over a long period of time, despite receiving evidence-based management in accordance with guideline, indicating that patients suffering from non-cardiogenic IS and who are receiving optimal management remain at considerable residual risks (RRs) responsible for the recurrence of cerebrovascular events. In addition to low-density lipoprotein cholesterol (LDL-C) and platelets, some new non-traditional parameters such as high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], peripheral circulating platelet-derived microvesicles, white blood cells-platelet complexes, NODlike receptor protein 3 (NLRP3) inflammasome, monomeric C-reactive protein, neutrophils and their products (neutrophil extracellular traps, NETs), may also be potential sources of RRs for recurrent IS. On the basis of the three pillars of secondary stroke prevention, namely, blood pressure reduction, lipid-lowering and antiplatelet therapy, the reduction in RRs may provide additional protection against recurrent IS. With this background, the identification and quantification of RRs associated with disease heterogeneity and individualized treatment strategies based on risk stratification are favorable in the mitigation of the huge stroke burden people unceasingly face.

Background: Insulin resistance is a phenomenon in which the lowering blood glucose capacity of insulin is decreased, which is a feature of type 2 diabetes mellitus. Some previous studies have found an association between insulin resistance and migraine. The triglyceride glucose (TyG) index is used to assess insulin resistance. However, there is no report on the association between the TyG index and migraine.

Objective: We present a cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) to clarify the association between the TyG index and migraine.

Methods: Data was acquired from the NHANES. Migraine was diagnosed based on patient selfreport and prescription medication. Data were analyzed using the weighted linear regression model, weighted chi-square test, logistic regression models, smooth curve fittings, and the twopiecewise linear regression model. Empower software was used for all data analysis.

Results: A total of 18704 participants were enrolled in this study, of which 209 were migraineurs. The rest were set as control. There was a statistically significant difference in mean age (p = 0.0222), gender (p < 0.0001), distribution of race (P < 0.0001), and drug usage between the two groups. However, there were no differences in type 2 diabetes mellitus, type 1 diabetes mellitus, total cholesterol, triglycerides, glucose, and TyG index between the two groups. According to logistic regression models, there was a linear relationship between TyG index and migraine in model 3 (odds ratio (OR = 0.54, p = 0.0165). particularly in female (OR= 0.51, p = 0.0202) or Mexican American (OR= 0.18, p = 0.0203). Moreover, there was no inflection point between the TyG index and migraine.

Conclusion: In conclusion, there was a linear relationship between the TyG index and migraine. A higher TyG index predicts a lower incidence of migraine, particularly in females and Mexican Americans. Meanwhile, there is no inflection point between the TyG index and migraine.

Aims: To explore angiopoietin-1 (Ang-1) involved in cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH) through its effect on endoplasmic reticulum stress (ERS) and apoptosis of vascular endothelial cells (VECs).

Background: CVS accounts for high morbidity and mortality of aSAH. Abnormal cellular physiological processes of VECs play a critical role in aSAH-induced CVS. In addition, Ang-1 is involved in regulating vascular structure and function.

Objective: To study the role of Ang-1 played in CVS and the underlying mechanism.

Methods: Blood samples of 130 aSAH patients were collected from 2016 to 2020 at West China Hospital of Sichuan University. A two-hemorrhage rodent model was employed to structure an aSAH-induced CVS rat model. Moreover, oxyHb was used to treat VECs to construct a CVS cell model in vitro. ELISA was used to measure the level of Ang-1 and HE staining to assess the rat's basilar arteries. Subsequently, CCK-8 was used to detect cell viability ability, and flow cytometry was used to test the cell apoptosis rate. Western blotting was used to determine the expression level of ERS marker and apoptosis-related proteins.

Results: There was an abnormally low expression of Ang-1 in CVS patients and CVS rats; besides, oxyHb treatment decreased Ang-1 in VECs in a concentration-dependent manner. Ang-1 treatment led to the thinner basilar artery wall and lumen circumference in CVS rats; moreover, in oxyHbtreated VECs, Ang-1 treatment inhibited ERS and apoptosis. In addition, the expression of p-PI3K and p-Akt in the CVS group decreased, while the expression of p53 in the CVS group increased. The expression of p-PI3K and p-Akt in 8 CVS rats negatively correlates with the expression of Ang- 1, but the correlation between p53 and Ang-1 was positive. Furthermore, the results suggested that Ang-1 suppressed ERS and apoptosis of VECs through the regulated PI3K/Akt/p53 pathway.

Conclusion: Elevated Ang-1 inhibited p53-mediated ERS and apoptosis of VECs through the activated PI3K/Akt pathway; Ang-1 might be an attractive treatment strategy for CVS.

Objective: Thrombectomy greatly improves the clinical prognosis of patients with acute ischemic stroke (AIS). The aim of this study is to develop a nomogram model that can predict the prognosis of patients with acute ischemic stroke undergoing thrombectomy.

Methods: We retrospectively collected information of patients with acute ischemic stroke who were admitted to the stroke Green Channel of the First Affiliated Hospital of Soochow University from September 2018 to May 2022. The main outcome was defined as a three-month unfavorable outcome (modified Rankin Scale 3-6). Based on the results of multivariate regression analysis, a nomogram was established. We tested the accuracy and discrimination of our nomogram by calculating the consistency index (C-index) and plotting the calibration curve.

Results: National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.418; 95% CI, 1.177-1.707; P＜0.001), low density lipoprotein cholesterol (LDL-C) (OR, 2.705; 95% CI, 1.203-6.080; P = 0.016), Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (OR, 0.633; 95% CI, 0.421-0.952; P = 0.028), infarct core volume (OR, 1.115; 95% CI, 1.043-1.192; P = 0.001) and ischemic penumbra volume (OR, 1.028; 95% CI, 1.006-1.050; P = 0.012) were independent risk factors for poor clinical prognosis of AIS patients treated with thrombectomy. The C-index of our nomogram was 0.967 and the calibration plot revealed a generally fit in predicting three-month unfavorable outcomes. Based on this nomogram, we stratified the risk of thrombectomy population. We found that low-risk population is less than or equal to 65 points, and patients of more than 65 points tend to have a poor clinical prognosis.

Conclusion: The nomogram, composed of NIHSS, LDL-C, ASPECTS, infarct core volume and ischemic penumbra volume, may predict the clinical prognosis of cerebral infarction patients treated with thrombectomy.

Background: Contrast extravasation (CE) on brain non-contrast computed tomography (NCCT) after endovascular therapy (EVT) is commonly present in patients with acute ischemic stroke (AIS). Substantial uncertainties remain about the relationship between the spatial location of CE and symptomatic intracranial hemorrhage (sICH). Therefore, this study aimed to evaluate this association.

Methods: We performed a retrospective screening on consecutive patients with AIS due to LVO (AIS-LVO) who had CE on NCCT immediately after EVT for anterior circulation large vessel occlusion (LVO). We used the Alberta stroke program early CT Score (ASPECTS) scoring system to estimate the spatial location of CE. Multivariable logistic regression was performed to achieve the risk factors of sICH.

Results: In this study, 115 of 153 (75.1%) anterior circulation AIS-LVO patients had CE on NCCT. After excluding 9 patients, 106 patients were enrolled in the final analysis. In multivariate regression analysis, atrial fibrillation (AF) (adjusted OR [aOR] 6.833, 95% confidence interval [CI] 1.331-35.081, P = 0.021) and CE-ASPECTS (aOR 0.602, 95% CI 0.411-0.882 P = 0.009) were associated with sICH. In subgroup analysis, CE at the internal capsule (IC) region was an independent risk factor for sICH (aOR 5.992, 95% CI 1.010-35.543 P < 0.05). These and conventional variables were incorporated as a predict model, with AUC of 0.899, demonstrating good discrimination and calibration for sICH in this study cohort.

Conclusion: The spatial location of CE on NCCT immediately after EVT was an independent and strong risk factor for sICH in acute ischemic stroke patients.

Background: Electroacupuncture (EA) treatment has been recommended by World Health Organization (WHO) for years on cerebral ischemia treatment, but the specific mechanism is still elusive. Studies have shown that EA can relieve brain damage after ischemic stroke by inhibiting programmed cell death (PCD), such as apoptosis, necroptosis, and autophagy. Ferroptosis, a unique form of cell death, has been highlighted recently and found to occur in I/R injury. We, therefore, investigated whether EA plays an essential role in relieving cerebral I/R injury via ferroptosis.

Methods: The modified MCAO/R rats model was established and then divided into four groups with or without EA treatment. Neurological deficit score and TTC staining were used to evaluate the neurological deficit and infarct volume of each group. Transmission electron microscope (TEM) and immunofluorescence staining were applied for mitochondrial ultrastructure and ROS accumulation observation, respectively. The proteins and mRNA expression of ACSL4, TFR1, and GPX4 were assessed by western blot and qPCR to detect the progress of ferroptosis.

Results: EA treatment improved neurological deficits and reduced infarct volume. Moreover, EA significantly relieved the mitochondrial morphological changes and inhibited ROS Production in MCAO rats. In terms of its mechanism, EA obviously decreased the ACSL4 and TFR1 expressions and promoted GPX4 levels in MCAO/R model rats.

Conclusion: These findings indicate that EA might play an essential role in relieving cerebral I/R injury via ferroptosis.

Objective: A balloon guide catheter (BGC) is widely used in mechanical thrombectomy (MT). However, the balloon inflation timing of BGC has not been clearly established. We evaluated whether balloon inflation timing of BGC affects the results of MT.

Methods: Patients who underwent MT with BGC for anterior circulation occlusion were enrolled. Patients were dichotomized into early and late balloon inflation groups, according to the timing of BGC inflation. Angiographic and clinical outcomes were compared between the two groups. Multivariable analyses were performed to evaluate the predictive factors for first-pass reperfusion (FPR) and successful reperfusion (SR).

Results: Of 436 patients, the early balloon inflation group showed a shorter procedure time (21 min (11-37) vs. 29 min (14-46), p = 0.014), a higher rate of SR with aspiration only (64.0% vs. 55.4%, p = 0.016), a lower aspiration catheter delivery failure rate (11.1% vs. 19.4%, p = 0.005), less frequent technique conversion (36.0% vs. 44.5%, p = 0.009), higher rate of FPR (58.2% vs. 50.2%, p = 0.011), and a lower rate of distal embolization (7.9% vs. 11.7%, P = 0.006), compared to the late balloon inflation group. In multivariate analysis, early balloon inflation was an independent predictor for FPR (odds ratio, OR 1.53, 95% confidence interval, CI 1.37-2.57; p = 0.011) and SR (OR 1.26, 95% CI 1.18-1.64; p = 0.018).

Conclusion: Early balloon inflation of BGC enables an effective procedure than late balloon inflation. Early balloon inflation was associated with higher rates of FPR and SR.

Background: Genome-wide association studies (GWAS) have been used to explore the connections between genotypes and phenotypes by comparing the genotype frequencies of genetic changes in individuals with similar origins but distinct traits.

Objectives: The aim is to employ the GWAS catalog to identify and investigate the various correlations between genotypes and phenotypes of the REST gene.

Methods: In this study, we utilized a large dataset of GWAS comprising 62,218,976 individuals in 112 studies and 122 associations with 122 traits (www.ebi.ac.uk/gwas/genes/REST) from European, Asian, Hispanic, African ancestry up to 28 February 2023. Protein-association network evaluation and gene ontology enrichment study was utilized to evaluate the biological function of the discovered gene modules.

Results: We identified several associations for both neurodevelopmental and neurodegenerative disorders linked to REST, as well as its mapped gene modules and their functional relationship networks.

Conclusion: This work offers fresh insights into identifying risk loci of neurological disorders caused by REST.