Translational Stroke Research最新文献

Our study aimed to investigate the factors associated with residual cavernous sinus extra-axial cavernous hemangiomas (ECHs) progression after surgery. This retrospective study consecutively included patients of cavernous sinus ECHs with incomplete lesion resection from February 2012 to January 2024. The progression of the lesions was defined as new lesions or a growth of residual lesion (≥ 10% increase in volume). Cox regression analysis was used to determine factors associated with residual lesion progression. Kaplan-Meier analysis was conducted to estimate the cumulative incidence of residual lesion progression. Sixty patients were included in this study. During the follow-up, there were 31 (51.7%) residual lesions underwent progression, whereas 29 (48.3%) patients were nonprogressive. Multivariate Cox analysis showed that the homogeneous enhancement lesion was correlated with the residual lesion progression (HR, 8.17 [95% CI, 1.03-64.58]; p = 0.046). Kaplan-Meier survival analysis indicated that the rate of homogeneous enhancement lesion progression (3.7 per 10 person-years) was significantly higher than that of the heterogeneous enhancement group (0.5 per 10 person-years; p = 0.019). Fourteen of the 31 patients with lesion progression underwent radiotherapy, and all of them experienced control over the progression of their lesions. This study found that end-of-treatment residual lesions are not rare in patients with cavernous sinus ECHs and the MRI feature is helpful to predict the progression of residual lesions.

Little is known about the association between periprocedural hemodynamics and in-stent restenosis (ISR) following stent implantation in patients with symptomatic intracranial atherosclerotic stenosis (ICAS). This study aims to identify periprocedural hemodynamics that may be associated with ISR. Subjects were selected from the NOVA trial (The First-in-man Trial Evaluating the Safety and Efficacy of the NOVA Intracranial Stent Trial). ISR was defined as greater than 50% stenosis of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. Periprocedural hemodynamics, including cerebral blood flow, cerebral blood volume, mean transit time, and time to peak (TTP), were derived from the time-density curve generated from digital subtraction angiography using the fast Fourier transform algorithm. Of the 263 patients enrolled in the NOVA trial, 176 with symptomatic high-grade ICAS who underwent stent implantation were included in this study. Of these, 35 (19.9%) were diagnosed with ISR at the one-year follow-up. No significant differences in pre-procedure hemodynamics were observed between stent groups and between the ISR groups and the non-ISR group. Higher post-procedure TTP (OR, 1.95; 95% CI, 1.26-3.02), the use of bare-metal stents (OR, 5.40; 95% CI, 2.21-13.19), and higher post-procedure residual stenosis (OR, 1.08; 95% CI, 1.03-1.13) were independent factors associated with ISR. Higher post-procedure TTP, the use of bare-metal stents, and higher post-procedure residual stenosis were independent factors associated with ISR. The combined use of periprocedural hemodynamics and clinical factors may help predict ISR in patients with symptomatic high-grade ICAS.

This study compares the clinical efficacy and outcomes of three surgical techniques-robot-assisted stereotactic assistance (ROSA), neuroendoscopy, and craniotomy-in the removal of intracranial hematomas in patients with cerebral hemorrhage affecting the basal ganglia. This retrospective study included 110 patients, who were grouped based on the surgical method used: 40 patients in the ROSA group, 50 in the craniotomy group, and 20 in the endoscopy group. We then compared the outcomes of the ROSA group with those of the craniotomy and endoscopy groups. Compared with the craniotomy group, the ROSA group had a significantly shorter operation time, higher hematoma clearance rate, lesser intraoperative blood loss, fewer postoperative pulmonary infections, and lower modified Rankin Scale (mRS) score at discharge and > 3 months after discharge. Compared with the endoscopy group, the ROSA group had a shorter operation time, lesser intraoperative blood loss, and fewer intraoperative blood transfusions. The ROSA robot provided superior surgical outcomes and patient prognoses compared to craniotomy and neuroendoscopy for the removal of intracranial hematomas in patients with basal ganglia cerebral hemorrhage.

Cerebral small vessel disease (CSVD) is a global brain disorder that is characterized by a series of clinical, neuroimaging, and neuropathological manifestations. However, the molecular pathophysiological mechanisms of CSVD have not been thoroughly investigated. Liquid chromatography-tandem mass spectrometry-based proteomics has broad application prospects in biomedicine. It is used to elucidate disease-related molecular processes and pathophysiological pathways, thus providing an important opportunity to explore the pathophysiological mechanisms of CSVD. Serum samples were obtained from 96 participants (58 with CSVD and 38 controls) consecutively recruited from The First Affiliated Hospital of Zhengzhou University. After removing high-abundance proteins, the serum samples were analyzed using high-resolution mass spectrometry. Bioinformatics methods were used for in-depth analysis of the obtained proteomic data, and the results were verified experimentally. Compared with the control group, 52 proteins were differentially expressed in the sera of the CSVD group. Furthermore, analyses indicated the involvement of these differentially expressed proteins in CSVD through participation in the overactivation of complement and coagulation cascades and dysregulation of insulin-like growth factor-binding proteins. The proteomic biomarker panel identified by the machine learning model combined with clinical features is expected to facilitate the diagnosis of CSVD (AUC = 0.947, 95% CI = 0.895-0.978). The study is the most in-depth study on CSVD proteomics to date and suggests that the overactivation of the complement cascade and the dysregulation of IGFBP on- IGF may be closely correlated with the occurrence and progression of CSVD, offering the potential to develop peripheral blood biomarkers and providing new insights into the biological basis of CSVD.

The role of chromatin biology and epigenetics in disease progression is gaining increasing recognition. Genes that escape X chromosome inactivation (XCI) can impact neuroinflammation through epigenetic mechanisms. Our previous study has suggested that the X escapee genes Kdm6a and Kdm5c are involved in microglial activation after stroke in aged mice. However, the underlying mechanisms remain unclear. We hypothesized that Kdm6a/5c demethylate H3K27Me3/H3K4Me3 in microglia, respectively, and mediate the transcription of interferon regulatory factor 5 (IRF5) and IRF4, leading to microglial pro-inflammatory responses and exacerbated stroke injury. Aged (17-20 months) Kdm6a/5c microglial conditional knockout (CKO) female mice (one allele of the gene) were subjected to a 60-min middle cerebral artery occlusion (MCAO). Gene floxed females (two alleles) and males (one allele) were included as controls. Infarct volume and behavioral deficits were quantified 3 days after stroke. Immune responses including microglial activation and infiltration of peripheral leukocytes in the ischemic brain were assessed by flow cytometry. Epigenetic modification of IRF5/4 by Kdm6a/5c was analyzed by CUT&RUN assay. The demethylation of H3K27Me3 by kdm6a increased IRF5 transcription; meanwhile, Kdm5c demethylated H3K4Me3 to repress IRF5. Both Kdm6a^fl/fl and Kdm5c^fl/fl mice had worse stroke outcomes compared to fl/y and CKO mice. Gene floxed females showed more robust expression of CD68 in microglia and elevated brain and plasma levels of IL-1β or TNF-α, after stroke. We concluded that IRF5 signaling plays a critical role in mediating the deleterious effect of Kdm6a, whereas Kdm5c's effect is independent of IRF5.

Introduction: Carotid artery stenting (CAS) and carotid endarterectomy (CEA) are gold-standard treatments of carotid artery stenosis. This study aims to identify the cost-effectiveness of CEA vs CAS.

Methods: Studies were screened through PubMed, MEDLINE, and Embase using PRISMA guidelines, and required ≥ 20 participants who were ≥ 16 years, alongside costs at 1-year postoperatively. The Shapiro-Wilk test, independent sample t-tests, ANOVA, and Spearman's R were used, with costs adjusted to 2024. A random-effects model was used to compare cost-effectiveness. Bias assessment was according to the Cochrane Risk of Bias 2.0 tool and the Newcastle-Ottawa Scale.

Results: 7 studies were included, with a sample of 6493 participants (3418 M, 3075 F). 2932 and 3511 participants underwent CEA and CAS respectively. CEA reported a significantly longer mean length of procedure (191.92 vs. 77.5 min, p < 0.0001) and length of stay (3.13 vs. 2.60 days, p < 0.0001) vs. CAS. The mean adjusted cost of CEA and CAS were $18156.60 (6466) and $17711.01 (5511) respectively. Studies reported lower risks of stroke (2.12% vs. 3.65%, p < 0.001), higher risks of myocardial infarctions (1.70% vs. 1.42%, p < 0.01), and higher risks of other complications for CEA vs. CAS respectively. The expected 1-year cost of CEA was marginally lower than CAS ($21264.03 vs. $21433.14, p < 0.05). The cost-effectiveness of CEA was marginally better than CAS (ratio = 1.019, 95% CI [1.017, 1.020)].

Conclusions: CEA provides marginally improved cost-effectiveness over CAS, providing long-term cost benefits to centers with large surgical volumes. However, shorter procedural times and inpatient stays with CAS may improve overall productivity. Cost should hence not be a deciding factor when choosing between CEA and CAS.

The etiology and mechanisms of ischemic stroke are complex, encompassing a variety of pathological processes including atherosclerosis, energy failure, neuroinflammation, blood-brain barrier damage, abnormal glial cell activation, and neuronal edema and necrosis. Endothelial cell-derived extracellular vesicles have garnered significant attention in various diseases, including ischemic stroke, owing to their widespread distribution, rich content, diverse functional sites, low immunogenicity, and ability to cross the blood-brain barrier. This study reviewed the current status of research on endothelial cell-derived extracellular vesicles and their roles and potential mechanisms in ischemic stroke. It aimed to elucidate the potential of these extracellular vesicles for clinical translation related to ischemic stroke, thereby providing new strategies and directions for treating patients with stroke. The findings indicated that endothelial cell-derived extracellular vesicles reduce the occurrence of stroke and improve post-stroke ischemic injury and prognosis through various mechanisms. Although studies have demonstrated the significant potential of endothelial cell-derived extracellular vesicles in treating ischemic stroke, their clinical translation remains challenging. Further research is needed to elucidate the specific roles of endothelial cell-derived extracellular vesicles in ischemic stroke, using additional in vitro or animal models. This will enable a more comprehensive assessment of the benefits and risks of endothelial cell-derived extracellular vesicles, thereby facilitating their clinical translation.

To investigate corticospinal tract (CST) injury and remodeling in patients with basal ganglia intracerebral hemorrhage (ICH) and explore the characterization capabilities of the corresponding parameters. In this prospective study, baseline, scale, and diffusion-weighted imaging (DWI) data were collected from patient cohorts. Participants were stratified into favorable (0-3 points) and unfavorable (4-6 points) prognosis groups, based on Modified Rankin Scale (mRS) after 3-6 months. The analysis of DWI data was conducted employing FSL and DSI Studio software to compare CST injury between the prognosis groups and CST remodeling features. A partial correlation model was deployed to elucidate the characterization capability of CST-related parameters. Additionally, logistic regression analysis was applied to identify factors significantly influencing prognosis. A total of 65 patients were enrolled with a mean age of 53.52 years and a median hematoma volume of 23.60 ml. The 44 patients were classified within the favorable prognosis group, demonstrating a statistically significant difference in their lower mean age (P = 0.002). Additionally, 10 patients underwent DWI review with a mean age of 50.30 years and a median hematoma volume of 18.56 ml. The investigation uncovered evidence of CST damage versus remodeling at the group level, respectively, with statistical significance (FDR-corrected P < 0.05, 10,000 permutations). The fractional anisotropy (FA) ratio in the internal capsule region exhibited moderate correlation with motor function (r = 0.507, P < 0.001) and the 3- to 6-month mRS scores (r =  - 0.318, P < 0.013). Furthermore, binary logistic regression analysis identified the FA rate in the internal capsule as a significant influencing factor of prognosis (odds ratio = 1.027, 95% confidence interval = 1.003-1.052, P = 0.025). Basal ganglia ICH can coincide with injury to the CST, which could undergo repair over time. Additionally, the FA ratio of the internal capsule is a potential biomarker to characterize residual motor function and provide prognostic information.

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms are known risk factors for vascular diseases due to the impact on folate metabolism dysfunction and homocysteine (Hcy) accumulation. This study aimed to investigate the association between folate metabolism risk and hemorrhagic risk in moyamoya disease (MMD). In this prospective study, we enrolled 350 MMD patients with complete genotype data for MTHFR and MTRR. Patients were divided into non-hemorrhagic and hemorrhagic MMD groups. Folate metabolism risk was classified into three levels according to genotype configurations. We analyzed the association between folate metabolism risk and hemorrhagic risk in MMD. Furthermore, the association between folate metabolism risk, collateral circulation, and periventricular anastomosis (PA) was assessed. In vitro experiments were conducted on HBMECs to explore the potential mechanism. TT genotype and T allele in MTHFR C677T were significantly associated with a lower risk of hemorrhage, whereas AC genotype and C allele in MTHFR A1298C were significantly linked to a higher risk of hemorrhage. Patients with high folate metabolism risk exhibited a significantly decreased risk of hemorrhage compared to those with low folate metabolism risk. Further analyses demonstrated that high folate metabolism risk was significantly correlated with poor collateral circulation and PA dilation and elevated levels of Hcy. In vitro experiments showed that increased Hcy levels significantly inhibited the proliferation, migration, and tube formation of HBMECs. This study identified a significant negative correlation between folate metabolism risk and hemorrhagic risk in MMD. URL: http://www.chictr.org.cn . Unique identifier: ChiCTR2200061889.

Background: In patients with symptomatic intracranial atherosclerotic stenosis (sICAS), recent evidence has suggested an association between artery-to-artery embolism (AAE) and cortical borderzone (CBZ) infarcts.

Methods: We recruited patients with 50-99% anterior-circulation sICAS in this cohort. Stroke mechanisms were categorized as isolated parent artery atherosclerosis occluding penetrating artery (PAO), isolated AAE, isolated hypoperfusion, and mixed mechanisms, using two classification systems. In Classification I, the probable stroke mechanisms of internal borderzone and CBZ infarcts were both hypoperfusion, which were respectively hypoperfusion and AAE in Classification II. Other classification criteria were the same. We investigated and compared the predictive values of the two systems in predicting 90-day and 1-year recurrent ischemic stroke in the same territory (SIT).

Results: Among 145 patients (median age 62 years), 101 (69.7%) were males. We found significant difference in the proportions of baseline stroke mechanisms between these two systems (p < 0.001). Eleven (7.6%) and 19 (13.1%) patients respectively had 90-day or 1-year recurrent SIT. Classification II better predicted the risk of 90-day recurrent SIT than Classification I, when patients were divided into 4 groups according to baseline stroke mechanisms (p = 0.029), or by the presence of hypoperfusion (p < 0.001). The two classification systems had comparable predictive values for 1-year recurrent SIT.

Conclusions: In medically treated sICAS patients, considering AAE rather than hypoperfusion as the stroke mechanism for CBZ infarcts could better predict early recurrent SITs.