AIM: The class I histone deacetylases (HDACs) implicate in microglial heterogenization and neuroinflammation following Intracerebral hemorrhage (ICH). Ferroptosis has also been reported in the ICH model. However, the relationship between HDAC1/2's role in microglial heterogenization and neuronal ferroptosis remains unclear.; METHODS: In both invivo and invitro models of ICH, we used Romidepsin (FK228), a selective HDAC1/2 inhibitor, to investigate its effects on microglial heterogenization and neuronal ferroptosis. In the invitro ICH model using Hemin, a transwell system was utilized to examine how microglia-driven inflammation and ICH-triggered neuronal ferroptosis interact. Immunostaining, Western blotting and RT-qPCR were used to evaluate the microglial heterogenization and neuronal ferroptosis. Microglial heterogenization, neuronal ferroptosis, and neurological dysfunctions were assessed invivo ICH mice model performed by autologous blood injection.; RESULTS: HDAC1/2 inhibition altered microglial heterogenization after ICH, as showing the reducing neuroinflammation and shifting microglia towards an anti-inflammatory phenotype by immunostaining and qPCR results. HDAC1/2 inhibition reduced ferroptosis, characterized by high ROS and low GPx4 expression in HT22 cells, and reduced iron and lipid deposition post-ICH invivo. Additionally, the Nrf2/HO1 signaling pathway, especially acetyl-Nrf2, activated in the invivo ICH model due to HDAC1/2 inhibition, plays a role in regulating microglial heterogenization. Furthermore, HDAC1/2 inhibition improved sensorimotor and histological outcomes post-ICH, offering a potential mechanism against ICH.; CONCLUSION: Inhibition of HDAC1/2 reduces neuro-ferroptosis by modifying the heterogeneity of microglia via the Nrf2/HO1 pathway, with a particular focus on acetyl-Nrf2. Additionally, this inhibition aids in the faster removal of hematomas and lessens prolonged neurological impairments, indicating novel approach for treating ICH. © 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Background: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are effective interventions for treating extracranial carotid artery stenosis (ECAS), but long-term prognosis is limited by postoperative restenosis. Carotid restenosis is defined as carotid stenosis >50% by various examination methods in patients after carotid revascularization. This retrospective cohort study examined the value of the triglyceride-glucose (TyG) index for predicting vascular restenosis after carotid revascularization. Methods: A total of 830 patients receiving CEA (408 cases, 49.2%) or CAS (422 cases, 50.8%) were included in this study. Patients were stratified into three subgroups according to TyG index tertile (high, intermediate, and low), and predictive value for restenosis was evaluated by constructing multivariate Cox proportional hazard regression models. Results: Incidence of postoperative restenosis was significantly greater among patients with a high TyG index according to univariate analysis. Kaplan-Meier survival curve analysis revealed a progressive increase in restenosis prevalence with rising TyG index. Multivariate Cox regression models also identified TyG index as an independent predictor of restenosis, while receiver operating characteristic (ROC) curve analysis showed that TyG index predicted restenosis with moderate sensitivity (57.24%) and specificity (67.99%) (AUC: 0.619, 95% CI 0.585-0.652, zstatistic=4.745, p<0.001). Addition of the TyG index to an established risk factor model incrementally improved restenosis prediction (AUC: 0.684 (0.651-0.715) vs 0.661 (0.628-0.694), z-statistic =2.027, p = 0.043) with statistical differences. Conclusion: The TyG index is positively correlated with vascular restenosis risk after revascularization, which can be used for incremental prediction and has certain predictive value.

BACKGROUND: Hemodynamic factors play an important role in aneurysm initiation, growth, rupture, and recurrence, while the mechanism of the hemodynamic characteristics is still controversial. A unique model of multiple aneurysms (initiation, growth, rupture, and recurrence) is helpful to avoids the confounders and further explore the possible hemodynamic mechanisms of aneurysm in different states.; METHODS: We present a model with multiple aneurysms, and including the states of initiation, growth, rupture, and recurrence, discuss the proposed mechanisms, and describe computational fluid dynamic model that was used to evaluate the likely hemodynamic effect of different states of the aneurysms.; RESULTS: The hemodynamic analysis suggests that high flow impingement and high WSS distribution at normal parent artery was found before aneurysmal initiation. The WSS distribution and flow velocity were decreased in the new sac after aneurysmal growth. Low WSS was the risk hemodynamic factor for aneurysmal rupture. High flow concentration region on the neck plane after coil embolization still marked in recanalized aneurysm.; CONCLUSIONS: Associations have been identified between high flow impingement and aneurysm recanalization, while low WSSis linked to the rupture of aneurysms. High flow concentration and high WSS distribution at normal artery associated with aneurysm initiation and growth, while after growth, the high-risk hemodynamics of aneurysm rupture was occurred, which is low WSS at aneurysm dome. © 2024. The Author(s).

BACKGROUND: Paraclinoid aneurysms, arising from the proximal dural ring and extending to the origin of the posterior communicating artery of the internal carotid artery (ICA), represent asignificant proportion of all intracranial aneurysms (IAs). Accurate prediction of the rupture risk of paraclinoid aneurysms is crucial for optimal management. The objective of this study was to identify risk factors for the rupture of paraclinoid aneurysms on the basis of computer-assisted semiautomated measurement (CASAM) and hemodynamics.; METHODS: The clinical, demographic and radiological data of the 304 paraclinoid aneurysms (285 unruptured and 19 ruptured) included were extracted from the Chinese Intracranial Aneurysm Project (CIAP) database. Morphological parameters were quantified via CASAM, and hemodynamic simulations were performed via computational fluid dynamics (CFD). Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for aneurysm rupture.; RESULTS: The mean age of the patients was 56.91±11.0 years, with afemale predominance (71.7%). Univariate analysis revealed that the undulation index (UI) and nonsphericity index (NSI) were significantly greater in ruptured paraclinoid aneurysms than in unruptured aneurysms. The proportion of ruptured paraclinoid aneurysms located laterally on the ICA was significantly lower than that of those located anteriorly (p=0.002). Multivariate logistic regression analysis revealed that agreater UI (OR=1.086, 95% CI 1.012-1.165; p=0.022) and larger low shear area (LSA) (OR=1.034, 95% CI 1.004-1.064; p=0.028) were independent risk factors for rupture.; CONCLUSIONS: Our findings indicate that agreater UI and alarger LSA are independent risk factors for the rupture of paraclinoid aneurysms. Compared with aneurysms in other orientations, paraclinoid aneurysms located anteriorly to the ICA are more prone to rupture. These findings may be useful in developing more consummate predictive models to enhance the management and surveillance of paraclinoid aneurysms in the future, leading to improved clinical decision-making and better patient outcomes. © 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

Background: Although stent-assisted coiling embolization (SAC) has been associated with a higher risk of ischemic and hemorrhagic complications, the use of SAC continues to rise for treating ruptured intracranial aneurysms (RIAs). This study aims to assess the safety and effectiveness of dual antiplatelet therapy (DAPT) in the context of RIAs.Methods: We conducted a retrospective analysis at a single center, involving patients with aneurysmal subarachnoid hemorrhage (aSAH) between May 1, 2017 and December 31, 2021. Patients were categorized into two groups: the SAC group and the non-SAC (NSC) group. Patients in the SAC group received DAPT. We compared modified Rankin Scale (mRS) score, along with hemorrhagic and ischemic complications, between the two groups to evaluate the safety and efficacy of DAPT for SAC.Results: The study included a total of 541 patients, of whom 38 (7.0%) experienced hemorrhagic complications and 48 (8.9%) developed ischemic complications. Additionally, 99 (18.3%) and 84 (15.5%) had poor clinical outcomes at discharge and 6 months, respectively. However, no statistically significant differences were observed between the two groups. Our analysis revealed that aneurysm location in the posterior circulation was a significant risk factor for an unfavorable prognosis when antiplatelet drugs were used following SAC ( p= 0.025).Conclusions: Administering antiplatelet drugs after SAC for RIAs has demonstrated both safety and effectiveness. However, caution should be exercised when considering this treatment strategy for RIAs located in the posterior circulation due to the potentially elevated risk.

BACKGROUND: Extracranial carotid artery aneurysm (ECCA) is an infrequent disease with an incidence of less than 1%. However, our understanding is still incomplete, and the preferred method to treat ECAA remains unknown.; METHODS: To share our initial experience with treatment options for large ECCAs. We have retrospectively included 15 patients who underwent treatment at our institution from 2015 to 2022. The treatment modality, patient demography, aneurysm morphology, and clinical and radiographic follow-data were collected and analyzed in all patients.; RESULTS: During the study period, 15 patients (with 19 ECCAs) were diagnosed and treated, of whom 8 (53.3%) were male. The average age of the patients was 53.6 years. The primary presenting symptoms was pulsatile neck mass (10/15, 66.7%). The etiology of ECAAs included atherosclerotic (6/15, 40.0%), infectious (3/15, 20.0%), and dissecting (1/15, 6.7%), and iatrogenic due to acupuncture (1/15, 6.7%). The mean±SD maximal diameter of the aneurysms was 23.8±14.1mm, with more than half of patients having aneurysms larger than 25mm (52.6%). 79.0% aneurysm had intraluminal thrombus at admission. Six patients underwent successful neurosurgical resection for a total of seven ECCAs. Five patients received endovascular interventional treatment. The remaining four patients who presented with seven ECCAs were placed under observation. The mean follow-up period was 28.1 months. Out of the patients who received treatment, it was discovered that 10 of them had completely occluded at the latest imaging study. During the course of conservative observation, it was observed that in one patient, the aneurysm disappeared and the parent vessel became thinner following anti-infection treatment. Out of all the patients, only one who was treated with Willis stent experienced a large area of cerebral infarction after treatment, which ultimately resulted in their death.; CONCLUSIONS: ECCA is rare and mostly present with mass effect. Neurosurgical treatment was more frequently feasible in large ECCAs, and endovascular surgery was the first choice for pseudoaneurysms and dissecting aneurysms. Anti-inflammation treatment was available for some infectious cases. © 2024. The Author(s).

BACKGROUND: Presently, a consistent strategy for determining the stability of unruptured intracranial aneurysms (UIAs) in elderly patients is lacking, primarily due to the unique characteristics of this demographic. Our objective was to assess the risk factors contributing to aneurysm instability (growth or rupture) within the elderly population.; METHODS: In this study, we compiled data from follow-up patients with UIAs spanning from November 2016 to August 2021. We specifically focused on patients aged≥60years. Clinical histories were gathered, and morphological parameters of aneurysms were measured. The growth of aneurysms was determined using the computer-assisted semi-automated measurement (CASAM). Growth and rupture rates of UIAs were calculated, and both univariate and multivariate Cox regression analyses were conducted. Additionally, Kaplan-Meier survival curves were plotted.; RESULTS: A total of 184 patients with 210 aneurysms were enrolled in the study. The follow-up period encompasses 506.6 aneurysm-years and 401.4 patient-years. Among all the aneurysms, 23 aneurysms exhibited growth, with an annual aneurysm growth rate of 11.0%, and 1 (4.5%) experienced rupture, resulting in an annual aneurysm rupture rate of 0.21%. Multivariate Cox analysis identified poorly controlled hypertension (P=0.011) and high-risk aneurysms (including anterior cerebral artery (ACA), anterior communicating artery (AcoA), posterior communicating artery aneurysm (PcoA), posterior circulation (PC)>4mm or distal internal carotid artery (ICAd), middle cerebral artery (MCA), and PC>7mm) (P=0.006) as independent risk factors for the development of unstable aneurysms.; CONCLUSIONS: In the elderly, poorly controlled hypertension and high-risk aneurysms emerge as significant risk factors for aneurysm instability. This underscores the importance of rigorous surveillance or timely intervention in patients presenting with these risk factors. © 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.

Background and purposeRecent observational studies have reported that serum total homocysteine (tHcy) is associated with intracranial aneurysms (IAs). However, the causal effect of tHcy on IAs is unknown. We leveraged large-scale genetic association and real-world data to investigate the causal effect of tHcy on IA formation. MethodsWe performed a two-sample Mendelian randomisation (MR) using publicly available genome-wide association studies summary statistics to investigate the causal relationship between tHcy and IAs, following the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology-MR statement. Furthermore, a propensity score matching (PSM) analysis was conducted to evaluate the detailed effects of tHcy on risk of IA formation by utilizing real-world multicentre data, including 9902 patients with and without IAs (1:1 matched). Further interaction and subgroup analyses were performed to elucidate how tHcy affects risk of IA formation. ResultsMR analyses indicated that genetically determined tHcy was causally associated with IA risk (OR, 1.38, 95% CI 1.07 to 1.79; p=0.018). This is consistent with the more conservative weighted median analysis (OR, 1.41, 95% CI 1.03 to 1.93; p=0.039). Further sensitivity analyses showed no evidence of horizontal pleiotropy or heterogeneity of single nucleotide polymorphisms in causal inference. According to the PSM study, we found that, compared with low tHcy (& LE;15 & mu;mol/L), moderate tHcy (>15-30 & mu;mol/L) (OR 2.13, 95% CI 1.93 to 2.36) and high tHcy (>30 & mu;mol/L) (OR 3.66, 95% CI 2.71 to 4.95) were associated with a higher IA risk (p trend <0.001). Subgroup analyses demonstrated significant ORs of tHcy in each subgroup when stratified by traditional cardiovascular risk factors. Furthermore, there was also a synergistic effect of tHcy and hypertension on IA risk (p interaction <0.001; the relative excess risk due to interaction=1.65, 95% CI 1.29 to 2.01). ConclusionBoth large-scale genetic evidence and multicentre real-world data support a causal association between tHcy and risk of IA formation. Serum tHcy may serve as a biomarker to identify high-risk individuals who would particularly benefit from folate supplementation.

Vertebrobasilar dolichoectasia (VBD) is a rare type of cerebrovascular disorder with high rates of morbidity and mortality. Due to the distinct pathological characteristics that fragmented internal elastic lamina and multiple dissections, VBD is difficult to treat and cured. Stent-assisted coil embolization is one of the main treatment modalities for such lesions. However, the duration of healing remained questionable, and there were no effective measures for evaluating endothelial coverage. Before complete endothelial coverage, the discontinuation of antiplatelet therapy may lead to fatal in-stent thrombosis; however, continued antiplatelet therapy could also result in bleeding complications. Thus, we present an autopsy case of late in-stent thrombosis due to the discontinuation of antiplatelet therapy and systematically review the literature to provide a reference for endovascular treatment and antiplatelet regimen of VBD.