Search

Previous studies have found that the peripheral immune environment is closely related to the occurrence and development of intracranial aneurysms. However, it remains unclear how the metabolism of peripheral blood mononuclear cells (PBMCs) and the composition of polymorphonuclear leukocytes (PMNs) changes in the process of intracranial aneurysm rupture. This study utilized cytometry by time of flight technology to conduct single‐cell profiling analysis of PBMCs and PMNs from 72 patients with IAs. By comparing the expression differences of key metabolic enzymes in PBMCs between patients with ruptured intracranial aneurysms (RIAs) and unruptured intracranial aneurysms, we found that most PBMCs subsets from RIA group showed upregulation of rate‐limiting enzymes related to the glycolytic pathway. By comparing the composition of PMNs, it was found that the proinflammatory CD101+HLA DR+ subsets were increased in the RIA group, accompanied by a decrease in the anti‐inflammatory polymorphonuclear myeloid‐derived suppressor cells. In conclusion, this study showed the changes in the peripheral immune profile of RIAs, which is helpful for our understanding of the mechanisms underlying peripheral changes and provides a direction for future related research. [ABSTRACT FROM AUTHOR]

Background: The fusiform aneurysm is a nonsaccular dilatation affecting the entire vessel wall over a short distance. Although PDGFRB somatic variants have been identified in fusiform intracranial aneurysms, the molecular and cellular mechanisms driving fusiform intracranial aneurysms due to PDGFRB somatic variants remain poorly understood. Methods: In this study, single-cell sequencing and immunofluorescence were employed to investigate the phenotypic changes in smooth muscle cells within fusiform intracranial aneurysms. Whole-exome sequencing revealed the presence of PDGFRB gene mutations in fusiform intracranial aneurysms. Subsequent immunoprecipitation experiments further explored the functional alterations of these mutated PDGFRB proteins. For the common c.1684 mutation site of PDGFRβ, we established mutant smooth muscle cell lines and zebrafish models. These models allowed us to simulate the effects of PDGFRB mutations. We explored the major downstream cellular pathways affected by PDGFRBY562D mutations and evaluated the potential therapeutic effects of Ruxolitinib. Results: Single-cell sequencing of two fusiform intracranial aneurysms sample revealed downregulated smooth muscle cell markers and overexpression of inflammation-related markers in vascular smooth muscle cells, which was validated by immunofluorescence staining, indicating smooth muscle cell phenotype modulation is involved in fusiform aneurysm. Whole-exome sequencing was performed on seven intracranial aneurysms (six fusiform and one saccular) and PDGFRB somatic mutations were detected in four fusiform aneurysms. Laser microdissection and Sanger sequencing results indicated that the PDGFRB mutations were present in smooth muscle layer. For the c.1684 (chr5: 149505131) site mutation reported many times, further cell experiments showed that PDGFRBY562D mutations promoted inflammatory-related vascular smooth muscle cell phenotype and JAK-STAT pathway played a crucial role in the process. Notably, transfection of PDGFRBY562D in zebrafish embryos resulted in cerebral vascular anomalies. Ruxolitinib, the JAK inhibitor, could reversed the smooth muscle cells phenotype modulation in vitro and inhibit the vascular anomalies in zebrafish induced by PDGFRB mutation. Conclusion: Our findings suggested that PDGFRB somatic variants played a role in regulating smooth muscle cells phenotype modulation in fusiform aneurysms and offered a potential therapeutic option for fusiform aneurysms. [ABSTRACT FROM AUTHOR]

Background: Intracranial aneurysms (IAs) represent a severe cerebrovascular disease that can potentially lead to subarachnoid haemorrhage. Previous studies have demonstrated the involvement of peripheral immune cells in the formation and progression of IAs. Nevertheless, the impact of metabolic alterations in peripheral immune cells and changes in neutrophil heterogeneity on the occurrence and progression of IAs remains uncertain. Methods: Single‐cell Cytometry by Time‐of‐Flight (CyTOF) technology was employed to profile the single‐cell atlas of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) in 72 patients with IAs. In a matched cohort, metabolic shifts in PBMC subsets of IA patients were investigated by contrasting the expression levels of key metabolic enzymes with their respective counterparts in the healthy control group. Simultaneously, compositional differences in peripheral blood PMNs subsets between the two groups were analysed to explore the impact of altered heterogeneity in neutrophils on the initiation and progression of IAs. Furthermore, integrating immune features based on CyTOF analysis and clinical characteristics, we constructed an aneurysm occurrence model and an aneurysm growth model using the random forest method in conjunction with LASSO regression. Results: Different subsets exhibited distinct metabolic characteristics. Overall, PBMCs from patients elevated CD98 expression and increased proliferation. Conversely, CD36 was up‐regulated in T cells, B cells and monocytes from the controls but down‐regulated in NK and NKT cells. The comparison also revealed differences in the metabolism and function of specific subsets between the two groups. In terms of PMNs, the neutrophil landscape within patients group revealed a pronounced shift towards heightened complexity. Various neutrophil subsets from the IA group generally exhibited lower expression levels of anti‐inflammatory functional molecules (IL‐4 and IL‐10). By integrating clinical and immune features, the constructed aneurysm occurrence model could precisely identify patients with IAs with high prediction accuracy (AUC = 0.987). Furthermore, the aneurysm growth model also exhibited superiority over ELAPSS scores in predicting aneurysm growth (lower prediction errors and out‐of‐bag errors). Conclusion: These findings enhanced our understanding of peripheral immune cell participation in aneurysm formation and growth from the perspectives of immune metabolism and neutrophil heterogeneity. Moreover, the predictive model based on CyTOF features holds the potential to aid in diagnosing and monitoring the progression of human IAs. [ABSTRACT FROM AUTHOR]

This article discusses a study that examined the impact of antihypertensive medication on the formation of intracranial aneurysms. The study found that antihypertensive drugs did not significantly reduce the formation of these aneurysms. However, the authors of the article raise some concerns about the study's methodology and suggest that further research is needed to clarify the relationship between antihypertensive medication and aneurysm formation. They propose that future studies should focus specifically on hypertensive patients with aneurysms and compare the incidence of aneurysm formation between those using antihypertensive drugs and those not using them. The authors also note a discrepancy in the data presented in one of the tables and suggest that further explanation is needed. Overall, the authors find the study interesting and meaningful, but believe that a redesign of the study is necessary to conclusively answer the research question. [Extracted from the article]

Background: Increasing evidence supports a critical role of chronic inflammation in intracranial aneurysm (IA). Understanding how the immunological alterations in IA provides opportunities for targeted treatment. However, there is a lack of comprehensive and detailed characterization of the changes in circulating immune cells in IA. Objective: To perform a comprehensive and detailed characterization of the changes in circulating immune cells in patients with IA. Methods: Peripheral blood mononuclear cell samples from IA patients (n = 26) and age-and sex-matched healthy controls (HCs, n = 20) were analyzed using high dimensional mass cytometry, and the frequency and phenotype of immune cell subtypes were assessed. Results: We identified 28 cell clusters and found that the immune signature of IA consists of cluster changes. IA patients exhibited dysfunction of immunity, with dysregulation of CD4+ T-cell clusters, increased B cells and monocytes, and decreased CD8+ T cells, DNT cells, and DPT cells. Moreover, compared with findings in HC, IA was associated with enhanced lymphocyte and monocyte immune activation, with a higher expression of HLA-DR, CXCR3, and CX3CR1. In addition, the expression of TLR4, p-STAT3, and the exhaustion marker PD1 was increased in T cells, B cells, and NK cells in IA patients. Conclusions: Our data provide an overview of the circulating immune cell landscape of IA patients, and reveal that the dysfunction of circulating immunity may play a potential role in the development of IA. [ABSTRACT FROM AUTHOR]

Rapid formation of innovative, inexpensive, personalized, and quickly reproducible artery bioresorbable stents (BRSs) is significantly important for treating dangerous and sometimes deadly cerebrovascular disorders. It is greatly challenging to give BRSs excellent mechanical properties, biocompatibility, and bioabsorbability. The current BRSs, which are mostly fabricated from poly-l-lactide (PLLA), are usually applied to coronary revascularization but may not be suitable for cerebrovascular revascularization. Here, novel 3D-printed BRSs for cerebrovascular disease enabling anti-stenosis and gradually disappearing after vessel endothelialization are designed and fabricated by combining biocompatible poly (p-dioxanone) (PPDO) and 3D printing technology for the first time. We can control the strut thickness and vessel coverage of BRSs by adjusting the printing parameters to make the size of BRSs suitable for small-diameter vascular use. We added bis-(2,6-diisopropylphenyl) carbodiimide (commercial name: stabaxol®-1) to PPDO to improve its hydrolytic stability without affecting its mechanical properties and biocompatibility. In vitro cell experiments confirmed that endothelial cells can be conveniently seeded and attached to the BRSs and subsequently demonstrated good proliferation ability. Owing to the excellent mechanical properties of the monofilaments fabricated by the PPDO, the 3D-printed BRSs with PPDO monofilaments support desirable flexibility, therefore offering a novel BRS application in the vascular disorders field. [ABSTRACT FROM AUTHOR]

Optimal microcatheter shaping is essential for successful endovascular coiling procedures which is sometimes challenging. Our aim was not only to introduce a new shaping method using three-dimensional (3D) printed vessel models but also to prove its feasibility, efficiency and superiority. This was a retrospective cohort study. From September 2019 to March 2021, 32 paraclinoid aneurysms managed with endovascular coiling were retrospectively included and identified. Sixteen aneurysms were coiled using 3D microcatheter shaping method (3D shaping group), and traditional manual shaping method using shaping mandrels was adopted for another 16 patients (control group). The cost and angiographical and clinical outcomes between the two groups were compared, and the feasibility and effectiveness of the new 3D shaping method were evaluated and described in detail. With technical success achieved in 93.75%, most of the 16 shaped microcatheters using new shaping method could be automatically navigated into the target aneurysms without the assistance of microguidewires and could be assessed with favorable accessibility, positioning and stability. Twenty-seven out of 32 aneurysms (84.38%) were completely occluded with the rate of perioperative complications being 12.50%. Although there was no significant difference between the occlusion rates and complication rates of the two groups, the new shaping method could dramatically decrease the number of coils deployed and reduce the overall procedure time. Patient specific shaping of microcatheters using 3D printing may facilitate easier and safer procedures in coil embolization of intracranial aneurysms with shorter surgery time and less coils deployed. [ABSTRACT FROM AUTHOR]

Objective: Paediatric aneurysms are rare and difficult to treat. Studies on the long-term angiographic and clinical outcomes conducted within the past decade are lacking. We aimed to investigate the clinical and radiographic outcomes of paediatric aneurysms treated with different strategies in a contemporary series. Methods: We performed a retrospective medical record review of paediatric patients examined at our institution between 2011 and 2018. Patient charts were retrospectively reviewed for age, presentation, type and location of the aneurysm, modalities of treatment, complications, and clinical and angiographic outcomes. The rates of aneurysm recurrence and de novo formation were determined. Results: We evaluated 61 patients (mean age, 11.6 years; 23 females, 38 males) with 69 intracranial aneurysms. Their presentations included headache, neurological deficits, aneurysmal subarachnoid haemorrhage, incidental aneurysm, and traumatic subarachnoid haemorrhage. Of the aneurysms, 30 (49.2%) were giant. Forty-five (73.8%) patients underwent treatment for their aneurysms, and 16 (26.2%) patients were managed conservatively. The perioperative morbidity rate was 17.8%. There were no deaths. The long-term morbidity rate was 4.6%. The clinical outcomes were favourable in 82.2 and 95.3% at discharge and follow-up, respectively (mean, 41.5 months; range, 1.5–9 years). For treated aneurysms, 2/43 (4.6%) risk of aneurysm recurrence, 1/43 (2.3%) risk of aneurysm bleeding, 1/43 (2.3%) risk of de novo aneurysm formation. The annual bleeding, recurrence, and de novo formation or growth risk were 0.7, 1.4, and 0.7%, respectively. Conclusions: In neurovascular centres where microsurgical and endovascular options are available, most children with intracranial aneurysms can be successfully treated with low morbidity and mortality. However, they have higher rates of recurrence and a greater risk of de novo formation or growth than their adult counterparts, which mandates lifelong follow-up. [ABSTRACT FROM AUTHOR]

Objective. Intracranial aneurysm (IA) is a fatal disease owing to vascular rupture and subarachnoid hemorrhage. Much attention has been given to circular RNAs (circRNAs) because they may be potential biomarkers for many diseases, but their mechanism in the formation of IA remains unknown. Methods. circRNA expression profile analysis of blood samples was conducted between patients with IA and controls. Overall, 235 differentially expressed circRNAs were confirmed between IA patients and the control group. The reliability of the microarray results was demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR). Results. Of 235 differentially expressed genes, 150 were upregulated, while the other 85 were downregulated. Five miRNAs matched to every differential expression of circRNAs, and related MREs were predicted. We performed gene ontology (GO) analysis to identify the functions of their targeted genes, with the terms "Homophilic cell adhesion via plasma membrane adhesion molecules" and "Positive regulation of cellular process" showing the highest fold enrichment. Conclusions. This study demonstrated the role of circRNA expression profiling in the formation of IA and revealed that the mTOR pathway can be a latent therapeutic strategy for IA. [ABSTRACT FROM AUTHOR]

In this study, we collected and analyzed 15 aneurysmal and 17 superficial temporal artery (STA) specimens from 32 Chinese patients with intracranial aneurysm. Total RNA was extracted and reverse transcribed to cDNA, and genome-wide expression profiling was performed by using the Affymetrix Human Genome U133 Plus 2.0 Array which allows a total number of 38,500 genes to be analyzed at the same time. Real-time RT-PCR was performed to verify the expression level of 8 selected genes. We found significant up-regulation of the TLR-2 gene. This result suggests that TLR-2 plays a key role in the formation of intracranial aneurysm in a Chinese population. To our knowledge, this study is the first to use the Human Genome U133 Plus 2.0 Array to analyze the gene expression profiles in Chinese patients with intracranial aneurysm. [ABSTRACT FROM AUTHOR]

Objective: A series of 2086 patients with cerebral arteriovenous malformations (AVMs) were reviewed and 635 patients underwent surgical treatment after 1992. Clinical characteristics and surgical results of patients with cerebral arteriovenous malformations (AVMs) were assessed. Methods: Collected data of 2086 consecutive AVM patients from January 1956 to October 2001 were analyzed. The size of the AVMs ranged from 1 to 9 cm. Patients who underwent surgical treatment were divided into two groups by date of admission: one was from 1992 to 1996 and the other was from 1997 to 2001. The variables assessed for clinical characteristics in our study included: age (at diagnosis), sex, Spetzler–Martin grade, first presentations. The surgical results were assessed by comparing the surgical complications between the two surgical groups. Difference between the two groups was assessed by χ2 test. Results: Cerebral AVMs are more commonly diagnosed at age 20 to 40 years. Hemorrhage (43.4%), headache (24.9%), and seizure (17.3%) were the first three common presentations. There was no difference in age distribution and sex ratio between the two surgical groups. Regarding Spetzler–Martin grading system, the percentage of grade 3 to 5 patients increased while that of grade 1 and 2 patients decreased (P=0.00). But the incidence of main surgical complications (death, hemiparalysis, cranial nerve dysfunction and gastrointestinal hemorrhage) was the same (P=0.796). Conclusions: Cerebral AVM is one of the important reasons for spontaneous intracranial hemorrhage in young patients. Spetzler–Martin grading system is helpful to predict the surgical risk. Microsurgical technique has made surgical treatment safer and become the best choice for cerebral AVM patients. Combination of intraoperative embolisation with surgical resection is a practical method in the treatment of giant cerebral AVMs. [Copyright &y& Elsevier]

Background Different gene expression profiles are observed in intracranial aneurysm tissues. Understanding these genes and what regulates their expression will provide insight into the pathogenesis of intracranial aneurysms. We investigated whether differences in DNA methylation regulate gene expression in intracranial aneurysms. Methods We compared 20 intracranial aneurysm tissue specimens with 20 matched specimens from the superficial temporal artery as controls. We identified the gene expression profiles in these samples using the GeneChip Human U133 Plus 2.0 array and evaluated DNA methylation modifications using the Infinium HumanMethylation450 BeadChip Kit. Results A total of 11,022 differentially methylated sites between aneurysm tissues and matched control tissues were identified, and 2142 differentially expressed gene transcripts were detected based on the 2 gene expression profiles. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and verification analysis showed that the MYH11 , LIFR , and TLR4 genes were associated with the occurrence and development of intracranial aneurysms. These genes mainly encode cell adhesion molecules or are involved in the NF-κB, JAK-STAT, and ERK/JNK signaling pathways. Conclusions In the development of intracranial aneurysms, DNA methylation plays an important role in the regulation of genetic expression involved in immune and inflammatory reactions, cell function, cell maintenance, and cell signal transduction. [ABSTRACT FROM AUTHOR]

Objective To study clinical outcome of giant intracranial aneurysms (diameter ≥25 mm) treated with different surgical modalities and to analyze factors affecting prognosis. Methods A retrospective analysis was performed of 204 consecutive patients with giant intracranial aneurysms who underwent surgical treatment in our department from 1995 to 2008. Clinical outcome was evaluated with the Glasgow Outcome Scale. Results Surgical modalities included direct aneurysm neck clipping in 102 patients (50.0%), parent artery reconstruction in 51 patients (25.0%), proximal artery ligation in 23 patients (11.3%; 4 patients combined with revascularization), trapping in 26 patients (12.7%), and wrapping in 2 patients (1.0%). Follow-up data were available for 181 patients (88.7%), with a mean follow-up period of 62 months (range, 12–164 months). A good outcome (Glasgow Outcome Scale score 5) was observed in 114 patients (63.0%), and a poor outcome (Glasgow Outcome Scale score 1–4) was observed in 67 patients (37.0%). Independent factors that affected prognosis were age and location of aneurysm. Older age (≥50 years) and location of aneurysm in posterior circulation were associated with poor outcome. In 85 patients with preoperative subarachnoid hemorrhage, patients with a higher Hunt and Hess grade (≥3) had a worse outcome compared with patients with a low Hunt and Hess grade (1 or 2). Surgical modalities and other factors were not significantly associated with clinical outcome. Conclusions Giant intracranial aneurysms are effectively treated with craniotomy and surgical treatment. Older age, aneurysm location in posterior circulation, and higher Hunt and Hess grade are risk factors affecting prognosis. [ABSTRACT FROM AUTHOR]

Objective . To screen differentially expressed proteins of saccular intracranial aneurysms and superficial temporal artery by the proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ) combined with reverse phase high-performance liquid chromatography. Methods . Collecting 17 samples from intracranial aneurysm patients undergoing aneurysmectomy as experiment group and 17 matched STA as control group. After quantification and enzymolysis of the protein, the iTRAQ were used to label the peptides of the 2 groups respectively. Then, the mixture of the peptides was fractioned by RP-HPLC and analyzed by LC-MS/MS to identify the differential expression proteins. Results . A total of 1699 proteins were identified from the ProteinPilot 4.5 software (AB SCIEX) using the Paragon database search algorithm. Comparing with STA, 54 proteins were significantly up-regulated (115:114 < 0.5-fold) and 37 were significantly down-regulated in sIAs (115:114 > 2.0-fold). Furthermore, Integrin β3, Secreted frizzled-related protein 2 were significantly up-regulated (2.3 fold and 2.1 fold, respectively), whereas MyosinIIb, Alpha-actinin-1, Laminin β2, and Carboxypeptidase A3 were down-regulated (3.01 fold, 2.1 fold, 2.07 fold, and 2.01 fold, respectively) in sIAs. GO Ontology analysis showed that most differential proteins expressed in cytoskeletal; up-regulated proteins in sIAs play an important role in inflammatory reaction, enzymatic hydrolysis, cell adhesion and invasion, and cellular immune reaction; down-regulated proteins in sIAs involved in cytoskeletal protein, enzyme, and structural protein. ITGB3, ACTN1 and MYL2 play a role in aneurysm formation via focal adhesion pathway. The results of Western-blot assay were consistent with the proteomic changes of those 6 proteins. Conclusion . The differentially expressed proteins in sIAs that showed aneurysm formation are related to cytoskeleton abnormal and extracellular matrix changes. The iTRAQ technology provides scientific foundation for the further study to explore the pathogenic mechanism of sIAs. [ABSTRACT FROM AUTHOR]

Background Intracranial aneurysm (IA) is a cerebrovascular disorder characterized by an abnormally bulged artery in the brain and subarachnoid hemorrhage caused by IA rupture with a high ratio of fatality and morbidity. However, the genetic cause of IA remains largely unknown. Methods A dysregulated long noncoding RNA (lncRNA) -associated competing endogenous RNA (ceRNA) network was constructed by using sample-matched microRNA (miRNA), lncRNA, and messenger (mRNA) expression profiles in 12 saccular IA samples and paired control arteries. Results In this study, 1150 lncRNAs, 2545 mRNAs, and 286 miRNAs were differentially expressed in IAs compared with control arteries. Using miRanda, a ceRNA score was assigned, and gene expression methods were used to construct a ceRNA network. The network consists of 8401 miRNA-lncRNA-mRNA interactions (199 miRNAs, 445 lncRNAs, 1116 mRNAs; P < 0.05). Further Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the mRNAs involved in the ceRNA network were involved in the regulation of muscle contraction and vascular smooth muscle contraction. Conclusions By comparing IAs and their control arteries, we identified differentially expressed lncRNAs, miRNAs, and mRNAs and suggested ceRNA roles in the pathogenesis of IA. These findings may help to characterize the pathogenesis of IA and provide novel therapeutic targets in the future for patients with IA. [ABSTRACT FROM AUTHOR]

Objective To gain comprehensive insight into the molecular mechanism of formation and rupture of intracranial aneurysms (IAs). Methods All publicly accessible microarray-based whole-genome gene expression profiles on IAs were retrieved. The significance analysis of microarrays method was applied to identify differentially expressed genes (DEGs). Functional annotation was performed using gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Expression of DEGs was examined using quantitative polymerase chain reaction. Results Six data sets of 3 microarray platforms were qualified and analyzed. Comparing expression profiles between aneurysmal wall and control vessels, 5232 significant DEGs were identified among 3 platforms, and MMP12 was shown to have the largest fold change of upregulation. In all 3 platforms, 46 DEGs were shared, and 1297 DEGs were commonly resolved in at least 2 microarray platforms. Among these 1297 concordant DEGs, the 512 upregulated genes were mainly enriched in inflammatory and immune response processes, whereas the 785 downregulated genes were primarily concentrated in smooth muscle cell contraction and development pathways. Comparison between expression profiles of ruptured and unruptured IAs revealed that a few angiogenic factors, including HIF1A , VEGFA , and ANGPTL4 , were upregulated in ruptured aneurysms. Subsequently, the upregulation of MMP12 , HIF1A , and VEGFA was partially confirmed using quantitative polymerase chain reaction among independent samples. Conclusions Inflammation, immune response, and loss of contractile vascular smooth muscle cells could potentially contribute to the formation of IAs, whereas the role of angiogenesis and vascular remodeling in IA formation and rupture needs further exploration. [ABSTRACT FROM AUTHOR]