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1.
J Transl Med ; 17(1): 349, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640726

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) accounts for 4.4% of cerebral vascular disease, which is one of the leading causes of death in China. Rupture of intracranial aneurysms (IAs) is the most common cause of SAH. The natural history of unruptured IAs (UIAs) and the risk factors for rupture are among the key issues regarding the pathogenesis of IA and SAH that remain unclear in the Chinese population. METHODS: The China Intracranial Aneurysm Project (CIAP) is a prospective, observational, multicenter registry study of the natural courses, risk factors for the onset and rupture, treatment methods, comorbidity management and other aspects of intracranial aneurysms. To date, there are five studies in the CIAP. CIAP-1 is a prospective observational cohort study of UIAs. More than 5000 patients who will be followed for at least 1 year are expected to be enrolled in this cohort. These participants come from more than 20 centers that represent different regions in China. Enrollment began on May 1, 2017, and will take approximately 5 years. A nationwide online database of UIAs will be built. Participants' basic, lifestyle, clinical and follow-up information will be collected. The blood samples will be stored in the Central Biological Specimen Bank. Strict standards have been established and will be followed in this study to ensure efficient implementation. DISCUSSION: The natural course of UIAs in the Chinese population will be explored in this registry study. In addition, the risk factors for the rupture of the UIAs and the joint effect of those factors will be analyzed. The present study aims to create a nationwide database of UIAs and investigate the natural course of UIAs in China. Trial registration The Natural Course of Unruptured Intracranial Aneurysms in a Chinese Cohort (ClinicalTrials.gov Identifier: NCT03117803). Registered: July 5, 2017.

2.
Front Neurosci ; 13: 645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293373

RESUMO

Previous studies have reported that the long non-coding RNA SNHG12 (lncRNA SNHG12) plays a critical role in regulating the function of mesenchymal stem cells (MSCs); however, the effect of lncRNA SNHG12 on MSCs in injured brain tissue has rarely been reported. We studied the effect and mechanism of lncRNA SNHG12-modified mesenchymal stem cells (MSCs) in treating brain injuries caused by ischemia/reperfusion (I/R). I/R treated rat brain microvascular endothelial cells (BMECs) were co-cultured with MSCs or I/R pretreated MSCs. Next, BMEC proliferation was detected by using CCK-8 and EdU assays, and cell apoptosis was determined by using flow cytometry and the Hoechst staining method. Autophagy of BMECs was determined using immunofluorescence and expression of associated pathway proteins were measured by western blotting. Moreover, BMEC proliferation, apoptosis, and autophagy were also determined after the BMECs had been co-cultured with shSNHG12-MSCs. In addition, a rat model of middle cerebral artery occlusion (MCAO) was used to further confirm the findings obtained with cells. I/R treatment significantly decreased the proliferation of BMECs, but increased their levels of SNHG12 expression, apoptosis, and autophagy. However, co-culturing of BMECs with MSCs markedly alleviated the reduction in BMEC proliferation and the increases in BMEC apoptosis and autophagy, as well as the phosphorylation of PI3K, AKT, and mTOR proteins in BMECs that had been induced by I/R. Furthermore, shSNHG12 remarkably enhanced the effects of MSCs. In addition, an injection MSCs reduced the infarct areas and rates of cell apoptosis in MACO rats, and reduced the phosphorylation of PI3K, AKT, and mTOR proteins. Moreover, shSNHG12 enhanced the ameliorative effect of MSCs in treating brain injuries in the MACO rats. In conclusion, silencing of SNHG12 enhanced the effects of MSCs in reducing apoptosis and autophagy of BMECs by activating the PI3K/AKT/mTOR signaling pathway.

3.
J Neurointerv Surg ; 11(11): 1162-1166, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31197025

RESUMO

OBJECTIVES: To characterize the safety and efficacy of large woven stents in the treatment of vertebrobasilar dolichoectasia (VBD). METHODS: We 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. RESULTS: The 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. CONCLUSIONS: Deployment of woven stents with or without supportive coiling may offer symptom relief and reconstruction in patients with VBD.


Assuntos
Procedimentos Endovasculares/instrumentação , Stents Metálicos Autoexpansíveis , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/terapia , Idoso , Embolização Terapêutica/instrumentação , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis/efeitos adversos , Resultado do Tratamento
4.
Front Neurol ; 10: 123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873104

RESUMO

Objective: Patients with poor-grade aneurysm subarachnoid hemorrhage (SAH) have commonly been considered to have a poor prognosis. The objective of this study was to investigate the independent risk factors affecting clinical outcomes in intracranial aneurysm patients with poor-grade aneurysm subarachnoid hemorrhage (aSAH) underwent different intervention therapies. Methods: A multicenter observational registry of 324 poor-grade aSAH patients treated at tertiary referral centers from October 2010 to March 2012 were enrolled in this study. The clinical data including patient characteristics on admission and during treatment course, treatment modality, aneurysm size and location, radiologic features, signs of cerebral herniation (dilated pupils), and functional neurologic outcome were collected. Clinical outcomes were assessed via a modified Rankin Scale at 12 months. Multivariate logistic regression models were used to develop prognostic models. The area under the receiver operator characteristic curves (AUC) and Hosmer-Lemeshow tests were used to assess discrimination and calibration. WAP score was developed to predict risk of poor outcome. Results: Older age, female gender, ventilated breathing status, non-reactive pupil response, pupil dilation, lower GCS score, a WFNS grade of V, intraventricular hemorrhage, a higher Fisher grade, a higher modified Fisher grade, and conservative treatment were calculated to be associated with a relatively poor outcome. Multivariate analyses revealed that older age, lower Glasgow coma scale score (GCS), the absence of pupillary reactivity, higher modified Fisher grade, and conservative treatment were independent predictors of poor outcome, showed good discrimination and calibration. Patients with WFNS grade V, older age and non-reactive pupillary reactivity were predicted to have a poor outcome by WAP risk score. Conclusions: A simple WAP risk score had good discrimination and calibration in the prediction of outcome. The risk score can be easily measured and may complement treatment decision-making.

5.
J Neuroinflammation ; 16(1): 8, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30646897

RESUMO

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.


Assuntos
Lesões Encefálicas/etiologia , Lesões Encefálicas/cirurgia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Receptor Notch1/metabolismo , Hemorragia Subaracnóidea/complicações , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Barreira Hematoencefálica/fisiopatologia , Lesões Encefálicas/diagnóstico por imagem , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade Capilar/fisiologia , Modelos Animais de Doenças , Fluoresceínas/farmacocinética , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Injeções Intraventriculares , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , RNA Interferente Pequeno/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptor Notch1/genética , Transdução de Sinais/fisiologia , Hemorragia Subaracnóidea/diagnóstico por imagem , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismo
6.
Eur Radiol ; 29(2): 689-698, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30019140

RESUMO

OBJECTIVES: 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. METHODS: 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. RESULTS: Univariate analyses showed that the WSS (p < 0.0001), angle between the A1 and A2 segments of the anterior cerebral artery (ACA) (p < 0.001), hypertension (grade II) (p = 0.007), fasting blood glucose (FBG; > 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). CONCLUSIONS: 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. KEY POINTS: • 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.


Assuntos
Artéria Cerebral Anterior/fisiopatologia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/fisiopatologia , Adulto , Idoso , Angiografia Digital , Artéria Cerebral Anterior/diagnóstico por imagem , Artéria Cerebral Anterior/patologia , Estudos de Casos e Controles , Angiografia Cerebral/métodos , Circulação Cerebrovascular/fisiologia , Estudos Transversais , Feminino , Hemodinâmica/fisiologia , Humanos , Imagem Tridimensional/métodos , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Estresse Mecânico , Ultrassonografia Doppler Transcraniana/métodos
7.
J Neurosurg ; 131(3): 868-875, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30265195

RESUMO

OBJECTIVE: Among 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. METHODS: One 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. RESULTS: Univariate 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). CONCLUSIONS: WSS 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.


Assuntos
Aneurisma Roto/etiologia , Aneurisma Roto/fisiopatologia , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/fisiopatologia , Resistência Vascular/fisiologia , Adulto , Idoso , Feminino , Humanos , Hidrodinâmica , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Risco
8.
J Transl Med ; 16(1): 263, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30257699

RESUMO

BACKGROUND: Ruptured aneurysms, the commonest cause of nontraumatic subarachnoid hemorrhage, can be catastrophic; the mortality and morbidity of affected patients being very high. Some risk factors, such as smoking, hypertension and female sex have been identified, whereas others, such as hemodynamics, imaging, and genomics, remain unclear. Currently, no accurate model that includes all factors for predicting such rupture is available. We plan to use data from a large cohort of Chinese individuals to set up a multidimensional model for predicting risk of rupture of unruptured intracranial aneurysms (UIAs). METHODS: The China Intracranial Aneurysm Project-2 (CIAP-2) will comprise screening of a cohort of 500 patients with UIA (From CIAP-1) and focus on hemodynamic factors, high resolution magnetic resonance imaging (HRMRI) findings, genetic factors, and biomarkers. Possible risk factors for rupture of UIA, including genetic factors, biomarkers, HRMRI, and hemodynamic factors, will be analyzed. The first project of the China Intracranial Aneurysm Project (CIAP-1; chaired by the Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China) will prospectively collect a cohort of 5000 patients with UIA from 20 centers in China, and collect baseline information for each patient. Multidimensional data will be acquired in follow-up assessments. Statistically significant clinical features in the UIA cohort will also be analyzed and integrated into the model for predicting risk of UIA rupture. After the model has been set up, the resultant evidence-based prediction will provide a preliminary theoretical basis for treating aneurysms at high risk of rupture. DISCUSSION: This study will explore the risk of rupture of aneurysms and develop a scientific multidimensional model for predicting rupture of unruptured intracranial aneurysms. Clinical Trials registration A Study on a Multidimensional Prediction Model for Rupture Risk of Unruptured Intracranial Aneurysms (CIAP-2), NCT03133624. Registered: 16 April 2017. https://clinicaltrials.gov/ct2/show/NCT03133624.


Assuntos
Aneurisma Roto/patologia , Aneurisma Intracraniano/patologia , Modelos Biológicos , Sistema de Registros , China , Humanos , Fatores de Risco
9.
J Neuroinflammation ; 15(1): 231, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30126439

RESUMO

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.


Assuntos
Anti-Inflamatórios/uso terapêutico , Moléculas de Adesão Celular/uso terapêutico , Polaridade Celular/efeitos dos fármacos , Encefalite/tratamento farmacológico , Microglia/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Moléculas de Adesão Celular/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalite/etiologia , Fluoresceínas/metabolismo , Injeções Intraventriculares , Masculino , Fosfopiruvato Hidratase/metabolismo , RNA Interferente Pequeno/uso terapêutico , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/complicações , Resultado do Tratamento
10.
Cell Death Dis ; 9(7): 767, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29991742

RESUMO

Sirtuin-1 (SIRT1), the mammalian ortholog of yeast Sir2p, is well known to be a highly conserved NAD+-dependent protein deacetylase that has been emerging as a key cancer target. Autophagy, an evolutionarily conserved, multi-step lysosomal degradation process, has been implicated in cancer. Accumulating evidence has recently revealed that SIRT1 may act as a tumor suppressor in several types of cancer, and thus activating SIRT1 would represent a possible therapeutic strategy. Thus, in our study, we identified that SIRT1 was a key prognostic factor in brain cancer based upon The Cancer Genome Atlas and tissue microarray analyses. Subsequently, we screened a series of potential small-molecule activators of SIRT1 from Drugbank, and found the best candidate compound F0911-7667 (hereafter, named Comp 5), which showed a good deacetylase activity for SIRT1 rather than other Sirtuins. In addition, we demonstrated that Comp 5-induced autophagic cell death via the AMPK-mTOR-ULK complex in U87MG and T98G cells. Interestingly, Comp 5-induced mitophagy by the SIRT1-PINK1-Parkin pathway. Further iTRAQ-based proteomics analyses revealed that Comp 5 could induce autophagy/mitophagy by downregulating 14-3-3γ, catalase, profilin-1, and HSP90α. Moreover, we showed that Comp 5 had a therapeutic potential on glioblastoma (GBM) and induced autophagy/mitophagy by activating SIRT1 in vivo. Together, these results demonstrate a novel small-molecule activator of SIRT1 that induces autophagic cell death/mitophagy in GBM cells, which would be utilized to exploit this compound as a leading drug for future cancer therapy.


Assuntos
Antineoplásicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Autofagia/efeitos dos fármacos , Autofagia/genética , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Profilinas/genética , Profilinas/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteômica , Sirtuína 1/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
11.
BMJ Open ; 8(5): e019333, 2018 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-29794089

RESUMO

INTRODUCTION: There are two approaches for the treatment of intracranial aneurysm (IA): interventional therapy and craniotomy, both of which have their advantages and disadvantages in terms of treatment efficacy. To avoid overtreatment of unruptured aneurysms (UIA), to save valuable medical resources and to reduce patient mortality and disability rate, it is vital that neurosurgeons select the most appropriate type of treatment to provide the best levels of care. In this study, we propose a refined, prospective, multicentre study for the Chinese population with strictly defined patient inclusion criteria, along with the selection of representative clinical participating centres. METHODS AND ANALYSIS: This report describes a multicentre, prospective cohort study. As IA is extremely harmful if it ruptures, ethical issues need to be taken into account with regard to this study. Researchers are therefore not able to use randomised controlled trials. The study will be conducted by 12 clinical centres located in different regions of China. The trial recruitment programme begins in 2016 and is scheduled to be completed in 2020. We expect 1500 participants with UIA to be included. Clinical information relating to the participants will be recorded objectively. The primary endpoints are an evaluation of the safety and efficiency of interventional treatment and craniotomy for 6 months after surgery, with each participant completing at least 1 year of follow-up. The secondary endpoint is the evaluation of safety and efficacy of interventional therapy and craniotomy clipping when participants are treated for 12 months. We also address the success of treatment and the incidence of adverse events. ETHICS AND DISSEMINATION: The research protocol and the informed consent form for participants in this study were approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University (2017-SJWK-001). The results of this study are expected to be disseminated in peer-reviewed journals in 2021. TRIAL REGISTRATION NUMBER: NCT03133598.


Assuntos
Aneurisma Intracraniano/terapia , Procedimentos Neurocirúrgicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto , China , Protocolos Clínicos , Craniotomia , Embolização Terapêutica , Feminino , Humanos , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Projetos de Pesquisa , Resultado do Tratamento , Adulto Jovem
12.
World Neurosurg ; 115: e218-e225, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29654957

RESUMO

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.


Assuntos
Aneurisma Roto/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Microvasos/diagnóstico por imagem , Vigilância da População , Adulto , Idoso , Aneurisma Roto/etiologia , Hemorragia Cerebral/complicações , Estudos Transversais , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/etiologia , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Estudos Retrospectivos
13.
Exp Ther Med ; 15(4): 3471-3476, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29616086

RESUMO

Intracranial 'kissing' aneurysms are rare types of multiple aneurysms referring to two adjacent aneurysms arising from identical or different arteries with separate origins and partially adherent walls. The present study reported a 54-year-old female patient, who was identified with a 'kissing' aneurysm in the A3 segment of the bilateral anterior cerebral arteries, as demonstrated by head computed tomography and emergency cerebral digital subtraction angiography analysis. In total, 12 days following the clipping of the aneurysms, the patient was discharged with a Modified Rankin Scale=0 and recovered well with no neurological deficits. Based on previous literature, it was indicated that the majority of patients with 'kissing' aneurysm have a good prognosis and the cure rate is as high as 96.8%. However, the recovery rate may not be that high as the sample size is not large enough to thoroughly demonstrate the complete prognosis of 'kissing' aneurysms.

14.
Front Neurosci ; 12: 96, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29535596

RESUMO

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) can lead to inflammation and neuronal dysfunction. There is a need for effective strategies to mitigate these effects and improve the outcome of patients who experience SAH. The mRNA-destabilizing protein tristetraprolin (TTP) is an anti-inflammatory factor that induces the decay of cytokine transcripts and has been implicated in diseases such as glioma. However, the mechanism of action of TTP in EBI after SAH is unclear. The present study investigated the effects of TTP regulation via phosphorylation in a rat model of SAH by protein phosphatase (PP)2A, which is a pleiotropic enzyme complex with multiple substrate phospho-proteins. We hypothesized that inhibitory phosphorylation of TTP by PP2A would reduce neuroinflammation and apoptosis. To evaluate the function of each factor, the PP2A agonist FTY720, short interfering (si)RNAs targeting TTP and PP2A were administered to rats by intracerebroventricular injection 24 h before SAH. Rats were evaluated with SAH grade, neurological score, brain water content and by western blotting, and terminal deoxynucleotidyltransferase dUTP nick-end labeling. We found that endogenous PP2A and TTP levels were increased after SAH. FTY720 induced PP2A activation would lead to dephosphorylation and activation of TTP and decreased production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8. SiRNA-mediated TTP knockdown abolished anti-inflammatory effects of FTY720 treatment, indicating that PP2A was associated with TTP activation in vivo. Decreased TNF-α, IL-6, and IL-8 levels were associated with improvement of neurological function, reduction of brain edema, suppression of caspase-3, and up-regulation of B cell lymphoma-2. These results demonstrated that PP2A activation could enhance the anti-inflammatory and anti-apoptotic effects of TTP, by which it might shed light on the development of an effective therapeutic strategy against EBI following SAH.

16.
Clin Neuroradiol ; 28(1): 17-24, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27154219

RESUMO

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.


Assuntos
Malformações Arteriovenosas Intracranianas/terapia , Microcirurgia , Resultado do Tratamento , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Embolização Terapêutica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiocirurgia , Estudos Retrospectivos , Adulto Jovem
17.
BMC Neurol ; 17(1): 214, 2017 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-29228923

RESUMO

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.


Assuntos
Predisposição Genética para Doença/genética , Aneurisma Intracraniano/genética , RNA Longo não Codificante/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
18.
Exp Ther Med ; 14(5): 3961-3970, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29067093

RESUMO

The present study reports the effect of successful treatment of cerebral venous sinus thrombosis (CVST) with stent retriever thrombectomy combined with local thrombolytic therapy. Medical records of 29 patients were retrospectively analyzed following a diagnosis of CVST with magnetic resonance venography (MRV) or digital subtraction angiography (DSA). Systemic anticoagulation was the initial treatment in all patients following admission. In group A, stent retriever thrombectomy combined with local thrombolytic therapy was performed on 14 patients who met the criteria of endovascular therapy. Stent-assisted angioplasty was also performed when patients presented with venous sinus stenosis. A total of 15 patients in group B received systemic anticoagulant treatment. Subsequently, warfarin was administered orally for 3 to 12 months as a continuous anticoagulant therapy. International normalized ratio was monitored when patients were receiving anticoagulant therapy. Additionally, clinical presentation, decision to escalate therapy, recanalization, Glasgow Coma Scale, modified Rankin Scale (mRS) and the clinical outcome was assessed. A total of 14 patients (9 female patients, 5 male patients), with ages ranging from 17 to 57 years, met the criteria of endovascular therapy. The clinical symptoms of 12 patients had improved after receiving endovascular therapy and only 2 patients suffered from intracranial hemorrhage following the procedure. Complete recanalization of venous sinus was exhibited in 10/14 (71.4%) patients in group A when compared with 1/15 (6.7%) patients in group B. mRS were improved in the 12-month follow-up in groups A and B when compared with that at admission. In the present study, patients with acute CVST treated with stent retriever thrombectomy combined with local thrombolytic therapy had a favorable outcome. To conclude, the present study provides a treatment option in treating CVST, particularly for patients that present with evident cortical venous outflow stasis or deteriorate neurology, despite appropriate anticoagulant therapy.

19.
Eur Radiol ; 27(11): 4730-4736, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28484825

RESUMO

OBJECTIVES: To characterise the safety, efficacy and cost of direct carotid-cavernous fistula (CCF) treatment using polyvinyl alcohol copolymer or detachable balloons. METHODS: 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. RESULTS: 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 < 0.001). CONCLUSIONS: Embolisation of CCF with polyvinyl alcohol copolymer is as safe and effective as detachable balloon but has a much higher cost and longer operation time. KEY POINTS: • Carotid-cavernous fistula results from a damaged carotid artery. • Detachable balloons have been used with success for many years. • Some reported excellent outcomes after embolisation with polyvinyl alcohol copolymer. • Treatment expense is much higher in the polyvinyl alcohol copolymer group.


Assuntos
Fístula Carotidocavernosa/terapia , Embolização Terapêutica/métodos , Polímeros/administração & dosagem , Álcool de Polivinil/administração & dosagem , Adolescente , Adulto , Idoso , Angiografia , Artéria Carótida Primitiva , Fístula Carotidocavernosa/diagnóstico por imagem , Custos e Análise de Custo , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Pain Physician ; 20(1): E127-E136, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28072804

RESUMO

BACKGROUND: Symptomatic headaches attributed to unruptured brain arteriovenous malformations (ubAVMs) are very common and affect patients' quality life, but multidisciplinary care of ubAVMs to improve symptomatic headache remains unclear. OBJECTIVE: The objective is to identify the features of symptomatic headaches, and to obtain headache outcomes following multidisciplinary care of ubAVMs, as well as provide background on the natural history of ubAVMs. STUDY DESIGN: The features of symptomatic headaches and headache outcomes were analyzed in a large cohort of cases after multidisciplinary care of ubAVMs. We have also provided information on the natural history of ubAVMs. SETTING: This study was conducted at the Department of Neurosurgery of Zhujiang Hospital where 336 patients from 1998 to 2014 were reviewed by a multidiscipline team. Only 124 patients were eligible. METHODS: The demographics, clinical features, imaging features, and headache details of eligible patients were reviewed. An 11-point pain scale score was used to assess symptomatic headaches before, during, and after treatment. The headache outcomes, death or stroke, and adverse functional outcomes (modified Rankin Scale score = 2, mRS = 2) were assessed following multidisciplinary care of ubAVMs. RESULTS: Twenty-three (56.1%) of 41 patients had migraine-like headaches located in occipital lobe (P < 0.001), while forty (63.5%) of 63 patients had tension-type-like headaches located in frontotemporal lobe (P < 0.001). For patients with tension-type-like or all types of headache, headache improvement differed between the multidisciplinary group and medical group (87.8% vs. 31.8%, P < 0.001; 85.7% vs. 40.7%, P < 0.001). The risk of death or stroke did not differ between multidisciplinary group and medical group (P = 0.393), whereas the risk of adverse functional outcome (mRS = 2) differed significantly by long-time follow-up (23.0% vs.10.0%, P = 0.022). LIMITATIONS: This study provides the initial experience to support multidisciplinary care for ubAVMs to improve symptomatic headaches and patients' quality life, but based on the retrospective study with inherent limitations, larger samples and multi-center trials are needed on this interesting issue. CONCLUSIONS: Occipital ubAVM is more likely to present with migraine-like headache, while frontotemporal ubAVM tends to present with tension-type-like headache. The effectiveness of multidisciplinary care for ubAVM to improve headache has been shown, but the natural history of ubAVM patients with headache remains unclear.Key Words: Unruptured brain arteriovenous malformations, headache, headache improvement, natural history.


Assuntos
Cefaleia/terapia , Malformações Arteriovenosas Intracranianas/terapia , Cefaleia/etiologia , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Estudos Retrospectivos , Resultado do Tratamento
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