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Hepatocellular carcinoma is one of the most common malignancies and leading cancer-associated deaths worldwide. Ozone has been proposed as a promising therapeutic agent in the treatment of various disorders. The purpose of this paper is to assess the potential anticancer effects of the ozone on liver cancer cells. The liver cancer cell line of bel7402 and SMMC7721 was used in this study. Proliferation was evaluated using the CCK-8 and the colony formation assay. Wond healing assay and transwell assay without Matrigel were used to evaluate their migration ability. Flow cytometry was used for cell cycle analysis and reactive oxygen species (ROS) determination. Glutathione detection kit was used for measurement of glutathione level. Protein expression was estimated by western blot analysis. Ozone treatment inhibited liver cancer cell proliferation, colony formation. Ozone induced G2/M phase cell cycle arrest, which could be elucidated by the change of protein levels of p53, p21, Cyclin D1, cyclin B1, cdc2, and CDK4. We also found that ozone treatment inhibited migration ability by inhibiting EMT-relating protein. Ozone also induced ROS accumulation and decreased glutathione level decreased, which contributed to the inactivation of the PI3K/AKT/NF-κB pathway. Finally, we found that pre-treatment of liver cancer cells with N-acetylcysteine resisted ozone-induced effects. Ozone restrains the proliferation and migration potential and EMT process of liver cancer cells via ROS accumulation and PI3K/AKT/NF-κB suppression.

Inflammation is known to play an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). T cell immunoglobulin and mucin domain-3 (Tim-3) has emerged as a critical regulator of adaptive and innate immune responses, and has been identified to play a vital role in certain inflammatory diseases; The present study explored the effect of Tim-3 on inflammatory responses and detailed mechanism in EBI following SAH. We investigated the effects of Tim-3 on SAH models established by endovascular puncture method in Sprague-Dawley rats. The present studies revealed that SAH induced a significant inflammatory response and significantly increased Tim-3 expression. Tim-3-AAV administration aggravated neurocyte apoptosis, brain edema, blood-brain barrier permeability, and neurological dysfunction; significantly inhibited Nrf2 expression; and increased HMGB1 expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-1 beta, IL-17, and IL-18. However, Tim-3 siRNA or NK252 administration abolished the pro-inflammatory effects of Tim-3. Our results indicate a function for Tim-3 as a molecular player that links neuroinflammation and brain damage after SAH. We reveal that Tim-3 overexpression deteriorates neuroinflammatory and neurocyte apoptosis after subarachnoid hemorrhage through the Nrf2/HMGB1 signaling pathway in rats.

Background: The prediction of aneurysm treatment outcomes can help to optimize the treatment strategies. Machine learning (ML) has shown positive results in many clinical areas. However, the development of such models requires expertise in ML, which is not an easy task for surgeons.Objectives: The recently emerged automated machine learning (AutoML) has shown promise in making ML more accessible to non-computer experts. We aimed to evaluate the feasibility of applying AutoML to develop the ML models for treatment outcome prediction.Methods: The patients with aneurysms treated by endovascular treatment were prospectively recruited from 2016 to 2020. Treatment was considered successful if angiographic complete occlusion was achieved at follow-up. A statistical prediction model was developed using multivariate logistic regression. In addition, two ML models were developed. One was developed manually and the other was developed by AutoML. Three models were compared based on their area under the precision-recall curve (AUPRC) and area under the receiver operating characteristic curve (AUROC).Results: The aneurysm size, stent-assisted coiling (SAC), and posterior circulation were the three significant and independent variables associated with treatment outcome. The statistical model showed an AUPRC of 0.432 and AUROC of 0.745. The conventional manually trained ML model showed an improved AUPRC of 0.545 and AUROC of 0.781. The AutoML derived ML model showed the best performance with AUPRC of 0.632 and AUROC of 0.832, significantly better than the other two models.Conclusions: This study demonstrated the feasibility of using AutoML to develop a high-quality ML model, which may outperform the statistical model and manually derived ML models. AutoML could be a useful tool that makes ML more accessible to the clinical researchers.

Background Activated microglia-mediated neuroinflammation has been regarded as an underlying key player in the pathogenesis of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). The therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) transplantation has been demonstrated in several brain injury models and is thought to involve modulation of the inflammatory response. The present study investigated the salutary effects of BMSCs on EBI after SAH and the potential mechanism mediated by Notch1 signaling pathway inhibition. Methods The Sprague-Dawley rats SAH model was induced by endovascular perforation method. BMSCs (3 × 106 cells) were transplanted intravenously into rats, and N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT), a Notch1 activation inhibitor, and Notch1 small interfering RNA (siRNA) were injected intracerebroventricularly. The effects of BMSCs on EBI were assayed by neurological score, brain water content (BWC), blood-brain barrier (BBB) permeability, magnetic resonance imaging, hematoxylin and eosin staining, and Fluoro-Jade C staining. Immunofluorescence and immunohistochemistry staining, Western blotting, and quantitative real-time polymerase chain reaction were used to analyze various proteins and transcript levels. Pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Results BMSCs treatment mitigated the neurobehavioral dysfunction, BWC and BBB disruption associated with EBI after SAH, reduced ionized calcium binding adapter molecule 1 and cluster of differentiation 68 staining and interleukin (IL)-1 beta, IL-6 and tumor necrosis factor alpha expression in the left hemisphere but concurrently increased IL-10 expression. DAPT or Notch1 siRNA administration reduced Notch1 signaling pathway activation following SAH, ameliorated neurobehavioral impairments, and BBB disruption; increased BWC and neuronal degeneration; and inhibited activation of microglia and production of pro-inflammatory factors. The augmentation of Notch1 signal pathway agents and phosphorylation of nuclear factor-κB after SAH were suppressed by BMSCs but the levels of Botch were upregulated in the ipsilateral hemisphere. Botch knockdown in BMSCs abrogated the protective effects of BMSCs treatment on EBI and the suppressive effects of BMSCs on Notch1 expression. Conclusions BMSCs treatment alleviated neurobehavioral impairments and the inflammatory response in EBI after SAH; these effects may be attributed to Botch upregulation in brain tissue, which subsequently inhibited the Notch1 signaling pathway. Electronic supplementary material The online version of this article (10.1186/s12974-019-1396-5) contains supplementary material, which is available to authorized users.

Inflammation is typically related to dysfunction of the blood-brain barrier (BBB) that leads to early brain injury (EBI) after subarachnoid hemorrhage (SAH). Resolvin D1 (RVD1), a lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and neuroprotective properties. This study investigated the effects and mechanisms of RVD1 in SAH. A Sprague-Dawley rat model of SAH was established through endovascular perforation. RVD1was injected through the femoral vein at 1 and 12 h after SAH induction. To further explore the potential neuroprotective mechanism, a formyl peptide receptor two antagonist (WRW4) was intracerebroventricularly administered 1 h after SAH induction. The expression of endogenous RVD1 was decreased whereas A20 and NLRP3 levels were increased after SAH. An exogenous RVD1 administration increased RVD1 concentration in brain tissue, and improved neurological function, neuroinflammation, BBB disruption, and brain edema. RVD1 treatment upregulated the expression of A20, occludin, claudin-5, and zona occludens-1, as well as downregulated nuclear factor-κBp65, NLRP3, matrix metallopeptidase 9, and intercellular cell adhesion molecule-1 expression. Furthermore, RVD1 inhibited microglial activation and neutrophil infiltration and promoted neutrophil apoptosis. However, the neuroprotective effects of RVD1 were abolished by WRW4. In summary, our findings reveal that RVD1 provides beneficial effects against inflammation-triggered BBB dysfunction after SAH by modulating A20 and NLRP3 inflammasome.

Background: Intracranial aneurysm wall degradation can be associated with lipid infiltration. However, the relationship between lipid infiltration and aneurysm rupture has not been explored quantitatively. To investigate the correlation between lipid infiltration and aneurysm rupture, we utilized patient-specific simulation of low-density lipoprotein (LDL) transport to analyze lipid infiltration in the cerebral aneurysm wall.Methods: Sixty-two aneurysms were analyzed. Patient blood pressure, plasma LDL concentration, and three-dimensional angiographic images were obtained to simulate LDL transport in aneurysms. Morphological, hemodynamic, and lipid accumulation parameters were compared between ruptures and unruptured groups. Multivariate logistic regression was also performed to determine parameters that are independently associated with rupture.Results: Size ratio, wall shear stress, low shear area, relative residence time, area-averaged LDL infiltration rate, and maximum LDL infiltration rate were significant parameters in univariate analysis (P < 0.05). Multivariate analysis revealed that only average LDL infiltration remained as a significant variable (P < 0.05). The prediction model derived showed good performance for rupture prediction (AUC, 0.885; 95% CI, 0.794–0.976).Conclusions: Ruptured aneurysms showed significantly higher LDL infiltration compared to unruptured ones. Our results suggested that lipid infiltration may promote aneurysm rupture. Lipid infiltration characteristics should be considered when assessing aneurysm rupture risk.

The study aimed to determine which hemodynamic parameters independently characterize anterior communicating artery (AcomA) aneurysm formation and explore the threshold of wall shear stress (WSS) of the parent artery to better illustrate the correlation between the magnitude of WSS and AcomA aneurysm formation. Eighty-one patients with AcomA aneurysms and 118 patients without intracranial aneurysms (control population), as confirmed by digital subtraction angiography (DSA) from January 2014 to May 2017, were included in this cross-sectional study. Three-dimensional-DSA was performed to evaluate the morphologic characteristics of AcomA aneurysms. Local hemodynamic parameters were obtained using transcranial color-coded duplex (TCCD). Multivariate logistic regression and a two-piecewise linear regression model were used to determine which hemodynamic parameters are independent predictors of AcomA aneurysm formation and identify the threshold effect of WSS of the parent artery with respect to AcomA aneurysm formation. Univariate analyses showed that the WSS (p 6.0 mmol/L) (p = 0.005), and dominant A1 (p < 0.001) were the significant parameters. Multivariate analyses showed a significant association between WSS of the parent artery and AcomA aneurysm formation (p = 0.0001). WSS of the parent artery (7.8-12.3 dyne/cm2) had a significant association between WSS and aneurysm formation (HR 2.0, 95% CI 1.3-2.8, p < 0.001). WSS ranging between 7.8 and 12.3 dyne/cm2 independently characterizes AcomA aneurysm formation. With each additional unit of WSS, there was a one-fold increase in the risk of AcomA aneurysm formation. • Multivariate analyses and a two-piecewise linear regression model were used to evaluate the risk factors for AcomA aneurysm formation and the threshold effect of WSS on AcomA aneurysm formation. • WSS ranging between 7.8 and 12.3 dyne/cm 2 was shown to be a reliable hemodynamic parameter in the formation of AcomA aneurysms. The probability of AcomA aneurysm formation increased one-fold for each additional unit of WSS. • An ultrasound-based TCCD technique is a simple and accessible noninvasive method for detecting WSS in vivo; thus, it can be applied as a screening tool for evaluating the probability of aneurysm formation in primary care facilities and community hospitals because of the relatively low resource intensity.

Background CDKN2BAS gene polymorphisms has been shown to correlation with intracranial aneurysm(IA) in the study of foreign people. The study, the author selected the Chinese people as the research object to explore whether CDKN2BAS gene polymorphisms associated with Chinese patients with IA. Methods We selected 200 patients(52.69 ± 11.50) with sporadic IA as experimental group, 200 participants(49.99 ± 13.00) over the same period to the hospital without cerebrovascular diseases as control group. Extraction of peripheral blood DNA, applying polymerase chain reaction(PCR)-ligase detection reaction (LDR) identified CDKN2BAS Single nucleotide polymorphism(SNP) locus genotype: rs6475606, rs1333040, rs10757272, rs3217992, rs974336, rs3217986, rs1063192. The differences in allelic and genotype frequencies between the patient and control groups were evaluated by the chi-square test or Fisher’s exact tests. Results The genotype of rs1333040 and rs6475606 shown association with sporadic IA(X2 = 8.545, P = 0.014; X2 = 10.961, P = 0.004; respectively);the C allele of rs6475606 showed reduction the occurrence of IA; the rs1333040 and rs6475606 associated with hemorrhage, the C allele of rs1333040 could lower the risk of hemorrhage, and rs6475606 will not, rs1333040 also associated with aneurysm size. Conclusion Our research shows that variant rs1333040 and rs6475606 of CDKN2BAS related to the Chinese han population of sporadic IAs occurs. This study confirms the association between CDKN2BAS and IAs.

ObjectivesTo characterize the safety and efficacy of large woven stents in the treatment of vertebrobasilar dolichoectasia (VBD).MethodsWe retrospectively reviewed 19 consecutive patients with VBD treated with large woven intracranial stent (Leo stents) between January 2016 and December 2018. The clinical symptoms and angiograms of all the patients were recorded.ResultsThe patients were treated with 1–3 large Leo stents (5.5 mm x 75 mm, 5.5 mm x 50 mm, or 4.5 mm x 40 mm), with or without coiling. They had follow-up angiography and MRI between 3 months and 1 year. Digital subtraction angiography showed 16 patients with complete reconstruction of the target vessels, one patient with almost complete reconstruction, and two patients with partial reconstruction. All patients had symptomatic improvement shortly after treatment, but two patients developed recurrent dysphagia at 8 and 18 months, respectively.ConclusionsDeployment of woven stents with or without supportive coiling may offer symptom relief and reconstruction in patients with VBD.

Background Early brain injury (EBI) refers to acute brain injury during the first 72 h after subarachnoid hemorrhage (SAH), which is one of the major causes of poor prognosis after SAH. Here, we investigated the effect and the related mechanism of TSG-6 on EBI after SAH. Materials and methods The Sprague-Dawley rat model of SAH was developed by the endovascular perforation method. TSG-6 (5μg) was administered by an intraventricular injection within 1.5 h after SAH. The effects of TSG-6 on EBI were assessed by neurological score, brain water content (BWC) and TUNEL staining. Immunofluorescence staining was used to assay NF-κB/p-NF-κB expression in microglia. Protein expression levels of heme oxygenase-1 (HO-1), NADPH oxidase 2 (Nox2), Bcl-2, Bax, and cleaved-caspase-3 were measured to investigate the potential mechanism. The enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the level of reactive oxygen species (ROS) were analyzed using commercially available kits. Results The results showed that TSG-6 treatment alleviated the neurobehavioral dysfunction and reduced BWC and the number of TUNEL-positive neurons in EBI after SAH. TSG-6 decreased the ROS level and enhanced the enzyme activity of SOD and GSH-Px after SAH. Furthermore TSG-6 inhibited the NF-κB activation, increased the protein expression levels of HO-1 and Bcl-2 and decreased the expression levels of Nox2, Bax, and cleaved-caspase-3. The administration of TSG-6 siRNA abolished the protective effects of TSG-6 on EBI after SAH. Conclusion We found that TSG-6 attenuated oxidative stress and apoptosis in EBI after SAH partly by inhibiting NF-κB and activating HO-1 pathway in brain tissue.

Objective Because the formation of associated aneurysms (AAs) related to the characteristics of cerebral artriovenous malformations (cAVMs) is poorly recognized, the purpose of this study was to identify the responsible characteristics of cAVMs related to the formation of AAs and to identify patients with responsible characteristics related to the formation of AAs through the analysis of the outcomes of these patients after treatment. Methods This study was performed to analyze the baseline characteristics of patients with cAVMs and AAs. The recurrent AA and residual size of cAVMs were used to evaluate the outcomes of patients after treatment. At the same time, the ROC curve was measured to gauge the relationship between the residual size of cAVMs and recurrent AAs in eligible patients. Results Fifty (15.0%) patients with cAVMs and AA were confirmed; these patients had twice the hazard of hemorrhage as patients with only isolated cAVMs. An infratentorial location ( P P = 0.002) were independent predictors of the formation of AAs. After a mean 22.7 months follow-up, 2 patients developed recurrent AAs, and the annual recurrence rate for patients with responsible characteristics was 17.6%, but for all patients was 7.2%. The ROC curve showed that patients, specifically patients with responsible characteristics, the residual size of the cAVM was closely related to recurrent AA (area = 0.89, 95% confidence interval 0.81−0.97, P = 0.023, cut-off value = 82.5%). Conclusions Patients with cAVMs and AA who harbor a fistula or an infratentorial location tend to form AAs. To prevent recurrent AAs and decrease the subsequent risk of hemorrhage, complete obliteration of cAVMs or retrograding over 80% size of cAVMs is recommended.

Preoperative embolization of meningiomas decreases intraoperative bleeding and shortens operation time. However, in meningiomas predominantly vascularized by the internal carotid artery (ICA) or vertebral artery (VA) branches, embolization of external carotid artery feeder branches may lead to a hemodynamic increase in blood supply from the ICA or VA, whereas embolization of ICA or VA feeder branches with particle embolic agents may be associated with complications. This study investigated the safety and efficacy of Glubran, a liquid embolic agent, for the embolization of this type of meningioma compared with polyvinyl-alcohol (PVA) particles.From January 2006 to June 2015, 157 consecutive patients (98 females; mean age = 48.3 years) who suffered from meningiomas and were preoperatively referred for embolization were retrospectively analyzed. Glubran (n = 40) and PVA (n = 55) were used to devascularize tumors. Sixty-two patients were not embolized because of dangerous anastomosis or other tumor characteristics. Intraoperative blood loss, intraoperative time, degree of angiographic devascularization and embolization-related complications were analyzed.The intraoperative blood loss and operative time were significantly lower in the Glubran-embolized versus non-embolized group. Furthermore, Glubran embolization significantly reduced intraoperative blood loss and operative time for meningiomas that received their primary blood supply from the ICA and/or VA compared with PVA embolization.Preoperative meningioma embolization with Glubran decreases intraoperative blood loss and operative time. Furthermore, embolization with Glubran produces more effective devascularization compared with PVA for meningiomas supplied by the ICA and/or VA. Thus, Glubran may represent a better embolic agent for this meningioma subtype.

Background An acute and drastic inflammatory response characterized by the production of inflammatory mediators is followed by stroke, including SAH. Overactivation of microglia parallels an excessive inflammatory response and worsened brain damage. Previous studies indicate that TSG-6 has potent immunomodulatory and anti-inflammatory properties. This study aimed to evaluate the effects of TSG-6 in modulating immune reaction and microglial phenotype shift after experimental SAH. Methods The SAH model was established by endovascular puncture method for Sprague–Dawley rats (weighing 280–320 g). Recombinant human protein and specific siRNAs for TSG-6 were exploited in vivo. Brain injury was assessed by neurologic scores, brain water content, and Fluoro-Jade C (FJC) staining. Microglia phenotypic status was evaluated and determined by Western immunoblotting, quantitative real-time polymerase chain reaction (qPCR) analyses, flow cytometry, and immunofluorescence labeling. Results SAH induced significant inflammation, and M1-dominated microglia polarization increased expression of TSG-6 and neurological dysfunction in rats. rh-TSG-6 significantly ameliorated brain injury, decreased proinflammatory mediators, and skewed microglia towards a more anti-inflammatory property 24-h after SAH. While knockdown of TSG-6 further induced detrimental effects of microglia accompanied with more neurological deficits, the anti-inflammation effects of rh-TSG-6 were associated with microglia phenotypic shift by regulating the level of SOCS3/STAT3 axis. Conclusions TSG-6 exerted neuroprotection against SAH-induced EBI in rats, mediated in part by skewing the balance of microglial response towards a protective phenotype, thereby preventing excessive tissue damage and improving functional outcomes. Our findings revealed the role of TSG-6 in modulating microglial response partially involved in the SOCS3/STAT3 pathway and TSG-6 may be a promising therapeutic target for the treatment of brain injury following SAH. Electronic supplementary material The online version of this article (10.1186/s12974-018-1279-1) contains supplementary material, which is available to authorized users.

Objective To determine whether the presence of cerebral microbleeds (CMBs) is independently associated with intracranial aneurysm rupture and to identify the time interval of CMB-related intracranial aneurysm rupture. Methods This cross-sectional study included 1847 patients with unruptured and ruptured intracranial aneurysms from January 2010 to November 2017. Clinical records and imaging, including T2-weighted gradient-recalled echo sequence magnetic resonance imaging that identified the presence of CMBs preoperatively, were evaluated. Univariate analysis and multivariate logistic regression were done to determine which parameters were independent factors for aneurysm rupture. The time interval of CMB-related intracranial aneurysm rupture was also evaluated. Results CMBs confirmed by magnetic resonance imaging were present in 142 patients (142/1847; 7.7%). Of 142 patients with CMBs, 56 patients (including 17 ruptured aneurysms) who received endovascular treatment and another 86 consecutive patients who did not receive embolization or surgery for various reasons were followed for 3–49 months. The incidence of CMB-related intracranial aneurysm rupture was 27.9% (24/86) during the follow-up period. The time interval of CMB-related intracranial aneurysm rupture was 3–27 months (median 9.5 months). Multivariate analyses showed CMBs were significantly correlated with intracranial aneurysm rupture (odds ratio = 1.6; 95% confidence interval, 1.1–2.4; P = 0.010). Conclusions CMBs were independently associated with intracranial aneurysm rupture. Patients with CMBs have a 60% increased risk of aneurysm rupture compared with patients without CMBs.

OBJECTIVEAmong clinical and morphological criteria, hemodynamics is the main predictor of aneurysm growth and rupture. This study aimed to identify which hemodynamic parameter in the parent artery could independently predict the rupture of anterior communicating artery (ACoA) aneurysms by using multivariate logistic regression and two-piecewise linear regression models. An additional objective was to look for a more simplified and convenient alternative to the widely used computational fluid dynamics (CFD) techniques to detect wall shear stress (WSS) as a screening tool for predicting the risk of aneurysm rupture during the follow-up of patients who did not undergo embolization or surgery.METHODSOne hundred sixty-two patients harboring ACoA aneurysms (130 ruptured and 32 unruptured) confirmed by 3D digital subtraction angiography at three centers were selected for this study. Morphological and hemodynamic parameters were evaluated for significance with respect to aneurysm rupture. Local hemodynamic parameters were obtained by MR angiography and transcranial color-coded duplex sonography to calculate WSS magnitude. Multivariate logistic regression and a two-piecewise linear regression analysis were performed to identify which hemodynamic parameter independently characterizes the rupture status of ACoA aneurysms.RESULTSUnivariate analysis showed that WSS (p < 0.001), circumferential wall tension (p = 0.005), age (p < 0.001), the angle between the A1 and A2 segments of the anterior cerebral artery (p < 0.001), size ratio (p = 0.023), aneurysm angle (p < 0.001), irregular shape (p = 0.005), and hypertension (grade II) (p = 0.006) were significant parameters. Multivariate analyses showed significant association between WSS in the parent artery and ACoA aneurysm rupture (p = 0.0001). WSS magnitude, evaluated by a two-piecewise linear regression model, was significantly correlated with the rupture of the ACoA aneurysm when the magnitude was higher than 12.3 dyne/cm2 (HR 7.2, 95% CI 1.5–33.6, p = 0.013).CONCLUSIONSWSS in the parent artery may be one of the reliable hemodynamic parameters characterizing the rupture status of ACoA aneurysms when the WSS magnitude is higher than 12.3 dyne/cm2. Analysis showed that with each additional unit of WSS (even with a 1-unit increase of WSS), there was a 6.2-fold increase in the risk of rupture for ACoA aneurysms.

Background/Aims: Prior studies demonstrated that pro-inflammatory cytokines (PICs) including IL-1β, IL-6 and TNF-α contribute to regulation of epilepsy-associated pathophysiological processes in the specific brain regions, namely the parietal cortex, hippocampus and amygdala. Moreover, GABA transporter type 1 and 3 (GAT-1 and GAT-3) modulating extracellular GABA levels are engaged in the role played by PICs in epileptogenesis. Note that brain ischemic injury also elevates cerebral PICs. Thus, in this report we examined the effects of nefiracetam (NEF), a pyrrolidone derivative, on the levels of IL-1β, IL-6 and TNF-α, and expression of GAT-1 and GAT-3 in the parietal cortex, hippocampus and amygdala using a rat model of post-ischemic nonconvulsive seizure (NCS). Methods: NCS was evoked by the middle cerebral artery occlusion (MCAO). ELISA and Western Blot analysis were employed to determine the levels of PICs and GAT-1/GAT-3, respectively. Results: MCAO significantly increased IL-1β, IL-6 and TNF-α in the parietal cortex, hippocampus and amygdala as compared with sham control animals (P

Aneurysm recurrence is a principle limitation of endovascular coiling procedures, especially in posterior communicating artery aneurysms, with reported recurrence rates of >30%. The adjunctive use of self-expandable stents has revolutionised the treatment of intracranial aneurysms, especially for complex morphologies, wide necks, or unfavourable dome-to-neck ratios. However, there are limited data concerning a direct comparison between simple coiling and stent-assisted coiling in posterior communicating artery aneurysms. This study aimed to compare the durability and outcomes of coiling versus stent-assisted coiling procedures. Imaging data of patients with posterior communicating artery aneurysms treated with coiling or stent-assisted coiling between January 2008 and October 2012 were retrospectively analysed. The initial angiographic results, procedural complications, and clinical outcomes were assessed at discharge. Imaging follow-up was performed with cerebral angiography. Complete aneurysm occlusion was achieved on initial angiography in 23/56 (41.1%) stent and 83/235 (35.3%) non-stent patients. At the latest follow-up (mean follow-up 14.3 ± 10.4 months for stent and 13.2 ± 9.5 months for non-stent patients), aneurysms had recurred in 5/47 (10.6%) stent and 57/203 (28.1%) non-stent patients (p = 0.014). Procedural complications occurred in 6/56 (10.7%) stent and 27/235 (11.5%) non-stent aneurysms. No rebleeding occurred during clinical follow-up (mean duration, 46.7 months). Recurrence rates at the latest follow-up were significantly lower in patients undergoing stent-assisted coiling than those undergoing simple coiling. Thus, use of the stent-assisted neck remodelling technique in the treatment of wide-necked posterior communicating artery intracranial aneurysms appears to improve the long-term clinical outcome.

Objective Imaging methods are essential in evaluating cerebral artery aneurysms and they have evolved with recent technical advances. Sixty-four-row multi-section computed tomography (64-MSCT) angiography and three-dimensional digital subtraction angiography (3D-DSA) are two of the most popular methods. We sought to systematically explore and find out which one would be better in imaging cerebral artery aneurysm, and try to investigate the potential use and value of 64-MSCT angiography and 3D-DSA in cerebral artery aneurysm. Method Followed by a predefined comprehensive literature search, we carefully searched both English and Chinese electronic databases for potentially relevant studies following our meta-analysis. Two reviewers independently assessed the methodological quality of the included eligible trials based on quality assessment of studies of diagnostic accuracy studies (QUADAS). Pooled summary statistics for sensitivity, specificity, positive and negative likelihood ratios (positive LR and negative LR), and diagnostic odds ratio (ORs) with their 95% confidence intervals (CIs) were utilized. Results Final meta-analysis of 923 cerebral artery aneurysm cases were incorporated from eight cohort studies and selected for statistical analysis. Pooled sensitivity and specificity of 64-MSCT angiography in the diagnosis of cerebral artery aneurysm were 0.97 (95% CI, 0.96–0.98) and 0.91 (0.88–0.94), respectively. The pooled positive LR was 7.68 (95% CI, 3.34–17.67); and the pooled negative LR was 0.04 (95% CI, 0.03–0.05). The pooled diagnostic OR was 263.69 (95% CI, 121.19–573.77). The area under the SROC curve was 0.9934 (standard error [SE] = 0.0031). No significant evidence of publication bias was detected ( P > 0.05). Conclusion The main finding of our meta-analysis revealed that 64-MSCT angiography relative to the 3D-DSA may have a high diagnostic accuracy for the cerebral artery aneurysm. Thus, 64-MSCT angiography may be an effective tool for the early detection of cerebral artery aneurysm.

To characterise the safety, efficacy and cost of direct carotid-cavernous fistula (CCF) treatment using polyvinyl alcohol copolymer or detachable balloons. We reviewed retrospectively patients with direct CCFs treated with either a detachable balloon or polyvinyl alcohol copolymer at our hospital from 2005 to 2015 and identified 94 patients with 105 CCFs. All patients had follow-up angiograms. The CCF occlusion rate, procedure complication rate, treatment expense and operation time were recorded. With a mean of 5.4 months of angiographic follow-up, the complete occlusion rate and recanalisation rate of the polyvinyl alcohol copolymer group was not significantly different from that of the detachable balloon group. The treatment expense was much higher and the operation time was much longer in the polyvinyl alcohol copolymer group than the detachable balloon group (P

The purpose of this study was to characterize clinical features and evaluate the clinical outcome of endovascular embolization treatment intracranial arteriovenous malformations in pediatric patients. A cohort of children (age ≤ 18 years) with arteriovenous malformations (AVMs) from 2000 to 2012 was included. Predictors studied included patient gender, age, and angioarchitectural features, including AVM location, nidus morphology and size, venous drainage, and associated aneurysms. Treatment method, complications and outcomes were recorded. The features of AVMs were evaluated before the treatment. One hundred twenty-seven children (77 males, mean age 13.2 years) were included; 90/127 (70.9 %) children were presented with hemorrhage. AVM size and deep venous drainage were independently associated with hemorrhage; 66/127 patients (52 %) treated with endovascular embolization. Complete obliteration at the end of all endovascular procedures was achieved in 14/66 patients (21.2 %), with an average of 78 % (range, 20–100 %) volume reduction. A mean of 2.9 (range, 1–9) feeding pedicles was embolized per patient. Overall, nine complications occurred in a total of 123 procedures (7.3 %). There was no procedure-related death in this study population. There was no significant difference between patients with and without complications in terms of AVM grade, demographic characteristics, or embolization features. AVM size and deep venous drainage were independently associated with hemorrhage in pediatric patients. Endovascular procedure is feasible and safe for pediatric AVMs, and complete embolization can be achieved in small AVMs, while large AVMs can be adequately reduced in size for additional microsurgery or stereotactic radiosurgery.

BACKGROUND AND PURPOSE: The incidence of unruptured intracranial aneurysms is increasing in the elderly population as life expectancy increases, and patients often present with headache. The goal of this study was to determine the effect of endovascular treatment on headache and identify factors associated with headache outcome in elderly patients with unruptured intracranial aneurysms. MATERIALS AND METHODS: A retrospective study was conducted for elderly patients (≥ 65 years old) being treated for unruptured intracranial aneurysms. Headache assessment was performed by a quantitative 11-point headache scale in all patients before and after endovascular treatment. Factors associated with headache outcome were investigated by univariate analyses. RESULTS: A total of 72 patients (mean age, 70.0 years; age range, 65–80 years; 41 women) fulfilled the inclusion criteria. There were 52 patients (72.2%) who presented with preoperative headache (headache score ≥ 1). Among them, 40 (76.9%) reported that headache score had an improvement according to their self-reported quantitative headache score after endovascular treatment. The average headache score was 5.63 preoperatively vs 2.50 postoperatively ( P = .000). Twenty patients (27.8%) had no headache before treatment (headache score = 0), of whom 2 (10.0%) reported new onset of headache postoperatively. Only a preoperative headache score was associated with treatment outcome of headache, and a higher headache score predicted a lack of headache relief after endovascular treatment ( P = .003). CONCLUSIONS: Endovascular coiling of unruptured intracranial aneurysms resulted in relief of headache in most of the elderly patients. Preoperative headache score was the only statistically significant predictor of headache outcome.

Previous studies have demonstrated that baicalein has protective effects against several diseases, which including ischemic stroke. The effect of baicalein on the blood-brain barrier (BBB) in intracerebral hemorrhage (ICH) and its related mechanisms are not well understood. We aimed to investigate the mechanisms by which baicalein may influence the BBB in a rat model of ICH. The rat model of ICH was induced by intravenous injection of collagenase IV into the brain. Animals were randomly divided into three groups: sham operation, vehicle, and baicalein group. Each group was then divided into subgroups, in which the rats were sacrificed at 24 and 72 h after ICH. We assessed brain edema, behavioral changes, BBB leakage, apoptosis, inducible nitric oxide synthase (iNOS), zonula occludens (ZO)-1, Mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB). Treatment with baicalein reduced brain water content, BBB leakage, apoptosis, and neurologic deficits, compared with vehicle. Baicalein also decreased ICH-induced changes in the levels of iNOS but increased the levels of ZO-1. The protective effect of baicalein on the BBB in ICH rats was possibly invoked by attenuated p-38 MAPK and JNK phosphorylation, and decreased activation of the NF-κB signaling pathway, which may have suppressed gene transcription, including iNOS, and eventually decreased formation of peroxynitrite (ONOO-). Our results suggest that baicalein exerts a protective effect on BBB disruption in the rat model of ICH. The likely mechanism is via inhibition of MAPKs and NF-κB signaling pathways, leading to decreased formation of iNOS and ONOO-, thereby improving neurological function.

The purpose of this study was to evaluate the safety and efficacy of transorbital puncture for the retreatment of previously embolized cavernous sinus dural arteriovenous fistulas (DAVFs) via a superior ophthalmic vein (SOV) approach.During a 12-year period, 9 consecutive patients with previously embolized cavernous sinus DAVFs underwent retreatment via the transorbital SOV approach.All of the nine cases of previously embolized cavernous sinus DAVFs were successfully embolized. Clinical follow-ups were conducted in all nine cases at the duration of 17-141 months (61.22 ± 39.13 months). No recanalization occurred during the follow-up period. A subtle ptosis appeared in two patients and disappeared in one of the two cases after a 4-year follow-up. One patient suffered from paroxysmal positional vertigo and bruit for nearly 2 years after the treatment, but the follow-up angiography demonstrated no recurrence. One patient had persistent visual impairment caused by the initial venous stasis retinopathy. One patient with a history of a procedure-related transient decrease in visual acuity had it return to the normal level. The remaining four cases had clear improvement in the ocular symptoms and became completely asymptomatic during the follow-up period. No patient worsened or developed new symptoms.The approach of surgical cannulation of the SOV for the retreatment of previously embolized cavernous sinus DAVFs was proved feasible and efficient, especially when the transarterial and transfemoral venous approaches were inaccessible. However, if the SOV is not dilated enough or is located deeply in the orbit, transorbital venous puncture access may not be possible.

Posterior fossa brain arteriovenous malformations (PFbAVM) are relatively rare brain disorders but have a high risk of hemorrhage. Endovascular embolization to reduce the lesion size before treatment may improve the outcome of PFbAVM. The purposes of this study were to identify risk factors associated with hemorrhage in PFbAVM and to assess clinical outcomes in patients receiving initial endovascular embolization. From 1999 to 2013 a total of 63 patients with PFbAVMs were treated (31 males and 32 females, 14.1 % of all AVM cases). A retrospective examination of patient demographics, clinical presentation, angiographic features, treatment modalities, complications and outcomes was carried out. The re-hemorrhage rate, obliteration rate and modified Rankin scale (MRS) were used as measures of outcome. Of the 63 PFbAVM patients 54 (85.7 %) exhibited hemorrhage and 15 had confirmed aneurysms. The cerebellar location (P = 0.007) and deep venous drainage (P = 0.012) were independent predictors of hemorrhage in multivariate analyses. The mean estimated devascularization was 46.9 % (range 10–100 %) in the 20 patients (31.7 %) treated by endovascular embolization. The 16 patients with residual niduses were further treated by radiosurgery, microsurgery or embolization. Complete obliteration was attained in 12 patients (67 %) while 2 (5.7 %) were left with persisting neurological deficits and 1 had a re-hemorrhage 3 years later (annual rate of 4.6 %). Favorable outcome (MRS ≤ 2) was obtained in the 20 patients receiving initial endovascular embolization (P = 0.039 versus preoperative MRS). Cerebellar location and deep venous drainage are predictors of hemorrhage in PFbAVM. Adjuvant endovascular embolization is useful and safe for PFbAVM prior to microsurgery or radiosurgery.

The purpose of this study was to analyze influencing factors associated with immediate angiographic results in intracranial aneurysms patients after endovascular treatment (EVT), providing theoretical evidence and guidance for clinical treatment of intracranial aneurysms. Totally 529 patients met the inclusive criteria, consisting of 338 males and 191 females. Gender; age; history of hypertension, diabetes, and smoking; intracranial atherosclerosis; rupture status, size and location, features of aneurysmal neck, shapes; vasospasm; treatment modality; and degree of aneurysm occlusion were all carefully and completely recorded. All data were investigated in univariate and multivariate logistic regression model to determine whether they were correlated with the degree of aneurysm occlusion. According to aneurysm size, aneurysms were classified as micro-miniature, miniature, and large aneurysms. There were 451 narrow-neck aneurysms and 78 wide-neck aneurysms. Totally 417 were regular and 112 were irregular. And 125 were un-ruptured aneurysms; 404 were ruptured aneurysms. The modalities of treatment were as follows: embolization with coil (n = 415), stent-assisted coil embolization (n = 89), and balloon-assisted coil embolization (n = 25). Univariate analysis showed that aneurysm size, feature of aneurysm neck, shape, and rupture status might affect the immediate occlusion after EVT. Multivariate logistic regression analysis indicated that ruptured aneurysm, tiny aneurysm, and wide-neck aneurysm were independent influencing factors of complete occlusion of intracranial aneurysm. Aneurysm rupture status, size, feature of aneurysmal neck, and shape might be the independent influencing factors of immediate angiographic results in intracranial aneurysm patients after EVT. Un-ruptured, micro-miniature, narrow-neck, and regular-shaped aneurysms were more probable to be occluded completely.

Background Isolated dissecting aneurysms of the posterior inferior cerebellar artery (PICA) are rare lesions, which carry high risk of rebleeding and mortality. However, the existing literature concerning predictors of outcome after endovascular treatment is limited and controversial. Our present study retrospectively reviewed and analyzed the clinical outcome of endovascular treatment–ruptured PICA-dissecting aneurysms and explored the predictors of outcome. Methods We retrospectively reviewed 17 consecutive patients with ruptured PICA dissecting aneurysms that underwent endovascular treatment from January 2003 to January 2014. Nine patients underwent selective coiling, whereas 7 patients underwent parent artery occlusion and 1 patient underwent stent-assisted coiling. Follow-up outcomes were evaluated using the modified Rankin Scale. The clinical outcomes of patients were categorized as favorable (modified Rankin Scale [mRS] score 0-1) or unfavorable (mRS score 2-6). Results Favorable outcomes (mRS score 0-1) were obtained in 13 of 17 patients. Post-treatment recurrence occurred in 1 patient with selective coiling in the 15-month follow-up, and the patient received stent-assisted coiling. The only patients with stent-assisted coiling developed PICA occlusion during follow-up. Aneurysm located in distal segment usually presented with intraventricular hemorrhage (P = .015). Hypertension, coexisting hydrocephalus, and time to operation (latter than 2 weeks) were associated with unfavorable outcome. Conclusions Endovascular treatment of isolated dissecting aneurysm of PICA had excellent clinical outcomes, hypertension, coexisting hydrocephalus, and time to operation (latter than 2 weeks), which were associated with unfavorable outcome. Long-term follow-ups are necessary to provide stronger conclusions.

The purpose of this study was to determine the safety and effectiveness of cerebellar arteriovenous malformations (AVMs) embolization and find out the suitable methods to manage associated aneurysms. Medical records of all patients between 1997 and 2014 with a diagnosis of cerebellar AVMs were retrospectively reviewed. Univariable and multivariable logistic analysis were used to assess AVMs characteristics to calculate for the risk of hemorrhage. Endovascular treatment was the main treatment measure to manage the AVMs and associated aneurysms. Of 142 patients, 115 (81.0 %) presented with hemorrhage and 42 (29.6 %) with associated aneurysms. A significant association with cerebellar AVMs hemorrhage was found for small size, prenidal aneurysms, and deep venous drainage in the univariable and multivariable analysis. Associated aneurysms were treated firstly in 41 patients except for 1 patient with 2 prenidal and 2 intranidal aneurysms. The special case was dealt with AVMs and 2 intranidal aneurysms first and angiography showed that the 2 prenidal associated aneurysms disappeared with time. Hemorrhage appeared in 13/142 patients (9.2 %) during the follow-up period, none of which was with associated aneurysms. Endovascular treatment can be a feasible way for treating cerebellar AVMs. Intranidal associated aneurysms should be treated first. Prenidal associated aneurysms can be treated later depending on the angioarchitecture of AVMs.

Transvenous embolization is the treatment of choice for cavernous sinus dural arteriovenous fistulas (csDAVFs) despite occasional difficulty in transvenous catheterization. We reported our experience in the treatment of csDAVFs by transarterial Onyx embolization in patients who had failed transvenous catheterization. We reviewed the clinical and radiographic records of csDAVFs patients receiving transarterial Onyx embolization after failed transvenous Onyx embolization at our institution over a period of 31 months. Success was defined as complete or near complete occlusion upon angiographic examination. In seven cases, the microcatheter failed to reach the cavernous sinus; in the remaining case, the internal jugular vein was occlusive. Eight sessions of the embolization and catheterization procedures via the arterial routes were conducted. Among them, five cases via the middle meningeal artery and the other three via the accessory meningeal artery. Angiography, immediately after embolization, revealed complete occlusion in seven cases (87.5 %) and partial occlusion in the remaining case. Angiographic follow-up (range, 6–10 months) showed that all patients achieved complete embolization. In cases where transvenous embolization of the cavernous sinus is difficult, transarterial embolization of the fistulas offers a safe and effective alternative.

Background Management of intracranial basilar dissecting aneurysms has been controversial and challenging, and surgical and conservative treatments usually have a bad prognosis. Our study aimed at evaluating the outcomes of endovascular treatment for these lesions and exploring the predictors of favorable outcome. Methods We retrospectively reviewed 50 consecutive patients with basilar dissecting aneurysms from January 2006 to January 2013. Twenty-four patients underwent stent-assisted coiling whereas 26 patients underwent conservative treatment. Follow-up outcomes were evaluated using modified Rankin Scale (mRS) score. Results Of the patients treated with stent-assisted coiling, 20 patients had a favorable outcome (mRS score, 0-1), post-treatment recurrence occurred in 3 patients, 1 had rebleeding, and 2 had no rebleeding. Of the patients treated with conservative therapy (observation or anticoagulation), 10 patients had an unfavorable outcome, 2 patients with ruptured aneurysms developed rebleeding, and 8 patients had poor outcome because of infarct progression. Stent-assisted coiling group had a more favorable outcome than the conservatively treated group (83.3% versus 55.2%, P = .019). Initial complete obliteration was related to the favorable outcome in endovascular-treated group ( P = .042). Stent placement was the only independent predictor of favorable outcome in the logistic regression analysis ( P = .030; odds ratio = 5.828; 95% confidence interval, 1.192-28.503). Conclusions Patients with basilar artery dissecting aneurysms treated with stent-assisted coiling had a more favorable outcome than the conservatively treated patients. Stent placement and initial complete occlusion were the favorable factors in patients with basilar dissecting aneurysm.

Treatment of giant/large internal carotid aneurysm is a challenge for neurologists. Previously, parent artery occlusion was the classic therapy; now the stent-assisted coil embolization has become available in recent years, but the optimal therapy is under debate. The goal of the present study was to compare two endovascular treatment modalities in terms of safety, efficacy and short-term outcomes.All the patients were divided into two groups: Group A: patients who underwent parent artery occlusion, and Group B: patients who underwent stent-assisted coil embolization. Follow-up outcomes were evaluated using the modified Rankin Scale (mRS).After 12 months of follow-up, the favorable outcome (mRS: 0-2) had no statistical significance in both groups (p = 1.00). Patients in group A had greater ischemia compared with patients in group B, but the difference did not reach statistical significance (p = 0.421). In group B, patients had a higher rate of partial occlusion (p = 0.255) and recurrence (10% vs. 0%; p = 0.586).Stent-assisted coiling may not be superior to parent artery occlusion in selected patients after short-term follow-up. Parent artery occlusion is a simple, safe and effective treatment for large/giant internal carotid aneurysms.

Objective: Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening disease and an animal model for in-depth study of CVST is needed. This study aimed to develop a rat model suitable for studying clinically relevant aspects of CVST and investigating its dynamic pathophysiological changes during a 7-day period. Method: A photothrombosis method was used to create a rat sinus-vein thrombosis model. A spot size-adjustable Diode Pumped Solid State laser (DPSS) combined with thrombin injection occluded the rostral and caudal superior sagittal sinus (SSS). The model was used to evaluate pathophysiological changes at different time points over 7 days. Evans Blue dye injection was used to detect alterations in blood–brain barrier (BBB) permeability. Brain water content was also measured. Moreover, we examined changes in brain infarct volume, neurological function, as well as histology after induction of CVST. Result: CVST in rats significantly altered BBB permeability, consistent with the development of brain edema. It was accompanied by an increase in brain infarct volume and deficits in neurological function that began on day 1, peaked on day 2, and typically improved by day 7 due to the neuroprotective effects of angiogenesis and gliocyte proliferation. Conclusion: In this study, we describe a rat model that produces clinically relevant pathophysiology and pathology that will facilitate evaluation of therapeutic regimens for CVST. Furthermore, our results indicate a period of optimal clinical intervention for patients with CVST, which may reduce the probability of dependency and death.

Summary Purpose The recovery time of traumatic carotid-cavernous fistula-induced oculomotor nerve paresis (ONP) after endovascular embolization with detachable balloons has not yet been adequately evaluated. This study was performed to make a deep analysis of the factors, which affect the prognosis of ONP after endovascular treatment of traumatic carotid-cavernous fistula (TCCF). Materials and methods We retrospectively evaluated the clinical characteristics and the outcome of oculomotor nerve function in a series of 98 consecutive patients with ONP due to traumatic carotid-cavernous fistula which were endovascular treated with detachable balloons. Univariate analysis was applied to test the association between the time of ONP recovery and clinical variables. Results Ninety-eight consecutive patients (62 males, 36 females, mean age 34.2 ± 12.7 years) having presented with ONP underwent endovascular treatment with detachable balloons were enrolled in this study. ONP was complete in 22 (22.4%) patients and partial in 76 (77.6%) patients. Ninety (91.8%) patients were successfully occluded by single-session endovascular embolization. Retreatments by transarterial routes had to be performed in 8 (8.2%) patients because of recurrent fistula having occurred within 4 weeks after embolization. ONP was recovered completely in all the patients, among who 4 (4.1%) were treated with occlusion of internal carotid artery. Factors showing significant association with the recovery time of ONP were the location of the fistula (P = 0.007), the degree of preoperative ONP (P = 0.003), the number of detachable balloon used (P = 0.000) and the length of ONP before endovascular treatment (P = 0.000). Conclusion Endovascular treatment of traumatic carotid-cavernous fistula-induced ONP with detachable balloons is a safe and effective method. The length of ONP before endovascular treatment, the location of the fistula, the degree of preoperative ONP, the number of detachable balloons used were the statistically significant predictors of the length of ONP complete recovery.