Microglia activation,classification and microglia-mediated neuroinflammatory modulators in subarachnoid hemorrhage

Subarachnoid hemorrhage is a devastating disease with significant mortality and morbidity,despite advances in treating cerebral aneurysms.There has been recent progress in the intensive care management and monitoring of patients with subarachnoid hemorrhage,but the results remain unsatisfactory.Microglia,the resident immune cells of the brain,are increasingly recognized as playing a significant role in neurological diseases,including subarachnoid hemorrhage.In early brain injury following subarachnoid hemorrhage,microglial activation and neuroinflammation have been implicated in the development of disease complications and recovery.To understand the disease processes following subarachnoid hemorrhage,it is important to focus on the modulators of microglial activation and the pro-inflammatory/anti-inflammatory cytokines and chemokines.In this review,we summarize research on the modulators of microglia-mediated inflammation in subarachnoid hemorrhage,including transcriptome changes and the neuroinflammatory signaling pathways.We also describe the latest developments in single-cell transcriptomics for microglia and summarize advances that have been made in the transcriptome-based classification of microglia and the implications for microglial activation and neuroinflammation.

Significant flow velocity reduction at the intracranial aneurysm neck after endovascular treatment leads to favourable angiographic outcome:a prospective study

Background With widely usage of flow diverter in intracranial aneurysm treatment,some previously used predictors may not be effective in evaluating the recurrence risk.We aimed to comprehensively re-evaluate the predictors of intracranial aneurysm outcome with various endovascular treatment methods and devices.Methods This is a prospective registered study.We analysed 6-month and 18-month follow-up angiographic data from the prospective study.Data on patient demographics,aneurysm morphology and type of treatment were recorded.Patient-specific haemodynamic simulations were performed.An unfavourable angiographic outcome was defined as recurrence of aneurysm in cases with coiling or stent-assisted coiling,patency of aneurysm in cases with flow diverters or retreatment during follow-up.Results In total,165 patients(177 intracranial aneurysms)with at least one angiographic follow-up data were analysed.For the short-term(6-month)results,after univariate analysis,the demographic,morphological and treatment-related factors did not achieve significantly statistical differences.The reduction ratio(RR)of velocity at aneurysm neck after embolisation was significantly lower in the unfavourable angiographic group than the favourable angiographic outcome group(p=0.002).After the Cox regression analysis,the RR of velocity at aneurysm neck was the only independent factor associated with favourable angiographic outcome(OR 0.028;p=0.001)and had an acceptable area under the curve(0.714)with a clear cut-off value(46.14%).Similarly,for the analysis of midterm(18-month)results,the RR of velocity at the aneurysm neck was the only independent significant factor for the unfavourable angiographic outcome(OR 0.050;p=0.017).The area under the curve was 0.754 and the cut-off value was 48.20%.Conclusions The haemodynamics showed an independent effect on angiographic follow-up results and may provide helpful suggestions for clinical practice in the future.

Endovascular treatment of bilateral intracranial vertebral artery aneurysms: an algorithm based on a 10- year neurointerventional experience

Background The management of bilateral intracranial vertebral artery dissecting aneurysms(IVADAs)is controversial,and requires the development of endovascular treatment modalities and principles.We aim to investigate the endovascular treatment strategy and outcomes of bilateral IVADAs.Methods We identified all bilateral IVADAs at a high-volume neurointerventional centre over a 10-year period(from January 2009 to December 2018).Radiographic and clinical data were recorded,and a treatment algorithm was derived.Results Twenty-seven patients with bilateral IVADAs(54 IVADAs in total,51 unruptured,3 ruptured)were diagnosed.Four patients(14.8%)received single-stage endovascular treatment,12 patients(44.4%)with staged endovascular treatment and 11 patients(40.8%)with unilateral endovascular treatment of bilateral IVADAs.Thirty-six IVADAs(85.7%)have complete obliteration at the follow-up angiography.Two of three ruptured IVADAs with stent-assisted coiling recanalised,and had further recoiling.Three patients(11.1%)have intraprocedural or postprocedural complications(two in single-stage and one in staged).Twenty-five patients(92.6%)had a favourable clinical outcome,and two patients(7.4%,all in single-stage)showed an unfavourable clinical outcome at follow-up.For the patients with unilateral reconstructive endovascular treatment,the contralateral untreated IVADAs were stable and had no growth or ruptured during follow-up period.None of all IVADAs had rebleeding during the clinical follow-up.Conclusions Endovascular treatment can be performed in bilateral IVADAs with high technical success,high complete obliteration rates and acceptable morbidity/mortality.Contralateral IVADAs had low rates of aneurysm growth and haemorrhage when treated in a staged/delayed fashion.

Statin treatment for unruptured intracranial aneurysms study: a study protocol for a double-blind, placebocontrolled trial

background and purpose A large proportion of patients with unruptured intracranial aneurysm(IA)are not suitable for surgical clipping and endovascular treatment.For these patients,anti-inflammatory medications are worth exploring due to inflammation of aneurysmal wall being a major factor in higher risk of rupture.Statin has been proven to reduce inflammation of atherosclerosis and maybe a suitable candidate.This study aimed to evaluate whether atorvastatin will reduce inflammatory of the aneurysm wall measured by the signal index of aneurysm wall enhancement.Methods and analysis The Statin Treatment for UnruptureD Intracranial anEurysms Study is a single-centre,phase 2,randomised,controlled,double-blind clinical trial.60 patients with unruptured IAs with aneurysm wall enhancement will be enrolled in Beijing Tiantan Hospital.The patients will be randomised to receive atorvastatin 20 mg or placebo orally per day for 12 months.The primary outcome will be the change in aneurysm wall enhancement measured by the signal index during the 12 months treatment with atorvastatin.The secondary study outcomes will be the change in aneurysm wall enhancement measured by the signal index at 3 months,the changes in aneurysmal morphology and inflammation-related factors(C reactive protein,tumour necrosis factor-α,interleukin-1βand interleukin-6)at 3 and 12 months.This study is the first to explore the role of atorvastatin in reducing inflammation in unruptured IA,which could lay the groundwork for future phase III trial.Ethics and dissemination Beijing Tiantan Hospital’s Ethics committee approved the research and written informed consents would be obtained from all participant or representative included in this study.

Efficient simulation of a low-profile visualized intraluminal support device: a novel fast virtual stenting technique

Background: The low-profile visualized intraluminal support (LVIS) stent has become a promising endovascular option for treating intracranial aneurysms. To achieve better treatment of aneurysms using LVIS, we developed a fast virtual stenting technique for use with LVIS (F-LVIS) to evaluate hemodynamic changes in the aneurysm and validate its reliability. Methods: A patient-specific aneurysm was selected for making comparisons between the real LVIS (R-LVIS) and the F-LVIS. To perform R-LVIS stenting, a hollow phantom based on a patient-specific aneurysm was fabricated using a three-dimensional printer. An R-LVIS was released in the phantom according to standard procedure. F-LVIS was then applied successfully in this aneurysm model. The computational fluid dynamics (CFD) values were calculated for both the F-LVIS and R-LVIS models. Qualitative and quantitative comparisons of the two models focused on hemodynamic parameters. Results: The hemodynamic characteristics for R-LVIS and F-LVIS were well matched. Representative contours of velocities and wall shear stress (WSS) were consistently similar in both distribution and magnitude. The velocity vectors also showed high similarity, although the R-LVIS model showed faster and more fluid streams entering the aneurysm. Variation tendencies of the velocity in the aneurysm and the WSS on the aneurysm wall were also similar in the two models, with no statistically significant differences in either velocity or WSS. Conclusions: The results of the computational hemodynamics indicate that F-LVIS is suitable for evaluating hemodynamic factors. This novel F-LVIS is considered efficient, practical, and effective.

Risk factors for periprocedural ischemic stroke following endovascular treatment of intracranial aneurysms

Background:The aim of this study was to comprehensively evaluate the risk factors of periprocedural ischemic stroke associated with endovascular treatment of intracranial aneurysms using a real-world database.Methods:From August 2016 to March 2017,167 patients were enrolled.Univariate analysis and multivariate logistic regression analysis were used to examine the risk factors for periprocedural ischemic stroke.Results:Among the 167 cases,periprocedural ischemic stroke occurred in 20 cases(11.98%).After univariate analysis,the ischemic group had a higher proportion of large(≥10 mm)aneurysms than the control group(45.0%vs.23.1%,p=0.036).The incidence of periprocedural ischemic stroke was higher in cases treated by flow diverter(21.6%)or stent-assisted coiling(11.8%)than in cases treated by coiling only(2.7%),and the differences were statistically significant(p=0.043).After multivariate logistic regression analysis,treatment modality was the independent risk factor for periprocedural ischemic stroke.Compared with the coiling-only procedure,flow diverter therapy was associated with a significantly higher rate of periprocedural ischemic stroke(OR 9.931;95%CI 1.174-84.038;p=0.035).Conclusions:Aneurysm size and treatment modality were associated with periprocedural ischemic stroke.Larger aneurysms were associated with increased risk of periprocedural ischemic stroke.Flow diverter therapy was associated with significantly more periprocedural ischemic stroke than the coiling procedure alone.

Hemodynamic analysis for endovascular treatment in small unruptured intracranial aneurysms:a matched comparison study of flow diverter versus LVIS

Background:We compared the treatment of small unruptured intracranial aneurysms(UIAs)with flow diverter and LVIS-assisted coiling to determine the effects of hemodynamic changes caused by different stent and coil packing in endovascular treatment.Methods:Fifty-one UIAs in 51 patients treated with pipeline embolization device(PED)were included in this study and defined as the PED group.We matched controls 1:1 and enrolled 51 UIAs who were treated with LVIS stent,which were defined as the LVIS group.Computational fluid dynamics were performed to assess hemodynamic alterations between PED and LVIS.Clinical analysis was also performed between these two groups after the match.Results:There was no difference in procedural complications between the two groups(P=0.558).At the first angiographic follow-up,the complete occlusion rate was significantly higher in the LVIS group compared with that in the PED group(98.0%vs.82.4%,P=0.027).However,during the further angiographic follow-up,the complete occlusion rate in the PED group achieved 100%,which was higher than that in the LVIS group(98.0%).Compared with the LVIS group after treatment,cases in the PED group showed a higher value of velocity in the aneurysm(0.03±0.09 vs.0.01±0.01,P=0.037)and WSS on the aneurysm(2.32±5.40 vs.0.33±0.47,P=0.011).Consequently,the reduction ratios of these two parameters also showed statistical differences.These parameters in the LVIS group showed much higher reduction ratios.However,the reduction ratio of the velocity on the neck plane was comparable between two groups.Conclusions:Both LVIS and PED were safe and effective for the treatment of small UIAs.However,LVIS-assisted coiling produced greater hemodynamic alterations in the aneurysm sac compared with PED.The hemodynamics in the aneurysm neck may be a key factor for aneurysm outcome.

Mutational spectrum of syndromic genes in sporadic brain arteriovenous malformation

Background:Brain arteriovenous malformations(BAVMs)are abnormal vessels that are apt to rupture,causing lifethreatening intracranial hemorrhage(ICH).The estimated prevalence of BAVMs is 0.05%among otherwise healthy individuals.In this study,we aim to investigate the mutational spectrum of syndromic genes in sporadic BAVM.Methods:We recruited a cohort of 150 patients with BAVM and performed whole-exome sequencing on their peripheral blood DNA.To explore the mutational spectrum of syndromic genes in sporadic brain arteriovenous malformation,we selected six genes according to the Online Mendelian Inheritance in Man(OMIM)and literature.All variants in the six candidate genes were extracted and underwent filtering for qualifying variants.Results:There are a total of four patients with rare variants in hereditary hemorrhagic telangiectasia-related genes.In addition,we identified two patients have the variant of RASA1 gene in our database,which are also rare mutations that are absent from population databases.However,we did not find any patients with GNAQ mutations in our database.Conclusions:In conclusion,we demonstrated that variants in syndromic vascular malformations play important roles in the etiology of sporadic BAVM.