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1.
Stroke ; 50(7): 1850-1858, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31167620

RESUMO

Background and Purpose- Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and a major cause of long-term disability. Recently, long noncoding RNAs have been revealed, which are tightly associated with several human diseases. However, the functions of long noncoding RNAs in ischemic stroke still remain largely unknown. In the current study, for the first time, we investigated the role of long noncoding RNA Nespas in ischemic stroke. Methods- We used in vivo models of middle cerebral artery occlusion and in vitro models of oxygen-glucose deprivation to illustrate the effect of long noncoding RNA Nespas on ischemic stroke. Results- We found expression of Nespas was significantly increased in ischemic cerebral tissues and oxygen-glucose deprivation-treated BV2 cells in a time-dependent manner. Silencing of Nespas aggravated middle cerebral artery occlusion operation-induced IR injury and cell death. In addition, proinflammatory cytokine production and NF-κB (nuclear factor-κB) signaling activation were inhibited by Nespas overexpression. TAK1 (transforming growth factor-ß-activated kinase 1) was found to directly interact with Nespas, and TAK1 activation was significantly suppressed by Nespas. At last, we found Nespas-inhibited TRIM8 (tripartite motif 8)-induced K63-linked polyubiquitination of TAK1. Conclusions- We showed that Nespas played anti-inflammatory and antiapoptotic roles in cultured microglial cells after oxygen-glucose deprivation stimulation and in mice after ischemic stroke by inhibiting TRIM8-related K63-linked polyubiquitination of TAK1.

2.
Neurosurg Focus ; 46(2): E8, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717073

RESUMO

OBJECTIVESymptomatic steno-occlusion of the proximal vertebral artery (VA) or subclavian artery (ScA) heralds a poor prognosis and high risk of stroke recurrence despite medical therapy, including antiplatelet or anticoagulant drugs. In some cases, the V2 segment of the cervical VA is patent and perfused via collateral vessels. The authors describe 7 patients who were successfully treated by external carotid artery (ECA)-saphenous vein (SV)-VA bypass.METHODSSeven cases involving symptomatic patients were retrospectively studied: 3 cases of V1 segment occlusion, 2 cases of severe in-stent restenosis in the V1 segment, and 2 cases of occlusion of the proximal ScA. All patients underwent ECA-SV-VA bypass. The ECA was isolated and retracted, and the anterior wall of the transverse foramen was unroofed. The VA was exposed, and then the 2 ends of the SV were anastomosed to the VA and ECA in an end-to-side fashion.RESULTSSurgical procedures were all performed as planned, with no intraoperative complications. There were 2 postoperative complications (severe laryngeal edema in one case and shoulder weakness in another), but both patients recovered fully and measures were taken to minimize laryngeal edema and its effects in subsequent cases. All patients experienced improvement of their symptoms. No new neurological deficits were reported. Postoperative angiography demonstrated that the anastomoses were all patent, and analysis of follow-up data (range of follow-up 12-78 months) revealed no further ischemic events in the vertebrobasilar territory.CONCLUSIONSThe ECA-SV-VA bypass is a useful treatment for patients who suffer medically refractory ischemic events in the vertebrobasilar territory when the proximal part of the VA or ScA is severely stenosed or occluded but the V2 segment of the cervical VA is patent.

3.
Stroke ; 50(3): 745-749, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30661491

RESUMO

Background and Purpose- We try to evaluate whether plaque features and perforator stroke after intracranial stenting is associated with the arterial remodeling patterns in patients with severe basilar artery stenosis. Methods- We studied patients with symptomatic intracranial arterial stenosis who underwent high-resolution magnetic resonance imaging from September 2014 to January 2017. Among them, patients with basilar artery stenosis underwent angioplasty and stenting were recruited. Arterial remodeling patterns were divided into negative or nonnegative remodeling. Plaque features were investigated by high-resolution magnetic resonance imaging, which includes plaque distribution, intraplaque hemorrhage, calcification, as well as enhancement patterns. Incidence of perforator strokes after intracranial stenting was recorded. Plaque features and incidence of poststenting perforator stroke were compared between negative and nonnegative remodeling. Results- Two hundred ninety-eight consecutive patients were enrolled. Among them, 30 patients fulfilled the inclusion criteria. There were 11 patients (36.7%) with negative remodeling and 19 (63.3%) with nonnegative remodeling. Twenty-six patients (86.7%) had diffuse distribution, 5 patients (16.7%) had intraplaque hemorrhage, 2 patients (6.7%) had calcification, and 17 patients (65.4%) had enhancement. Three patients had perforator stroke after stenting. Plaque features were similar between negative and nonnegative remodeling groups. Patients with negative remodeling were more likely to have perforator stroke after stenting comparing with patients with nonnegative remodeling (27.3% versus 0%, P=0.041). Conclusions- Perforator stroke after basilar artery stenting may be related to negative remodeling on high-resolution magnetic resonance imaging. The finding needs to be confirmed in future studies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02705599.

4.
Clin Neuroradiol ; 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30498847

RESUMO

PURPOSE: To investigate the predictors for good outcome of endovascular therapy (EVT) for patients with acute vertebrobasilar artery occlusion (VBAO) due to intracranial atherosclerosis stenosis (ICAS). METHODS: From April 2012 to February 2018, patients with VBAO due to ICAS who received EVT were retrospectively analyzed. ICAS was defined as fixed stenosis of >70%, or a degree of fixed stenosis >50% in addition to either perfusion impairment or evidence to re-occlusion. Good outcome was defined as mRS≤2 at 90 days. Both logistic regression and receiver operating characteristic curve (ROC) analyses were performed to explore the predictors. RESULTS: Among 103 patients enrolled in the analysis, 40.8% achieved good outcome. Prior antiplatelet therapy (OR, 7.301; 95% CI, 1.761-30.265; P=0.006), EVT+IVT (OR, 7.343; 95% CI, 1.621-33.263; P=0.010 ), the pc-ASPECT on DWI (OR, 1.705; 95% CI, 1.127-2.580; P=0.012), BATMAN (OR, 1.395; 95% CI, 1.005-1.937; P=0047), general anesthesia (OR, 0.081; 95% CI, 0.010-0.633; P=0.017), onset-to-recanalization time (≤542min vs. >542min) (OR, 0.194; 95% CI, 0.057-0.661; P=0.009) and the initial NIHSS (OR, 0.882; 95% CI, 0.820-0.949; P=0.001) were significantly associated with good outcome in logistic regression. Based on ROC analyses, initial NIHSS score (area under the curve [AUC]= 0.816, p <0.001; cutoff,19.5; sensitivity, 78.7%; specificity, 72.5%) was significant predictors of good outcome. CONCLUSIONS: For patients with VBAO due to ICAS, prior antiplatelet therapy, EVT+IVT, local anesthesia, short onset-to-recanalization time, a low initial NIHSS, a high pc-ASPECT and BATMAN might be helpful to predict the good outcome at 90 days after EVT.

5.
Interv Neuroradiol ; : 1591019918811800, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514143

RESUMO

BACKGROUND: Therapeutic strategies and outcomes vary with stroke subtypes for patients with acute vertebrobasilar occlusion (VBAO). This study aimed to compare characteristics and outcomes of VBAO due to intracranial atherosclerotic disease (ICAD) and embolisms and identify baseline predictors of ICAD. METHODS: Patients with VBAO who received endovascular therapy (EVT) were retrospectively analyzed. Participants fulfilling the criteria were classified as the ICAD group (focal stenosis of >70%, or fixed stenosis >50% in addition to either flow and perfusion impairment on angiography or an evident reocclusion tendency) and the embolism group (defined as no evidence of focal significant stenosis after thrombolysis or thrombectomy). Baseline characteristics and outcomes after EVT were compared between the two groups, and logistic regression was performed to explore the factors associated with ICAD. RESULTS: Among the 133 patients enrolled, 95 (71.4%) patients were categorized in the ICAD group, and 38 (28.6%) in the embolism group. A history of atrial fibrillation (odds ratio (OR) 0.142; 95% confidence interval (CI) (0.028-0.707), p = 0.017), distal basilar artery occlusion (OR 0.107; 95% CI (0.040-0.289), p < 0.001) and V4 segment occlusion (OR 3.423; 95% CI (1.172-9.999), p = 0.024) were independently associated with ICAD. Patients with VBAO due to ICAD had a lower rate of recanalization (81.1% vs 100%, p = 0.004), but the 90-day good clinical outcome was comparable (41.1% vs 50.0%, p = 0.347). CONCLUSIONS: The occlusion sites and a history of atrial fibrillation might be helpful in predicting ICAD in patients with VBAO. Patients with ICAD who were treated by EVT had a lower rate of recanalization but comparable 90-day good outcomes.

6.
Neuroradiology ; 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30488258

RESUMO

PURPOSE: The aim of our study is to report the peri-procedural complications and long-term stroke recurrent rate of symptomatic intracranial atherosclerosis (ICAS) patients who underwent submaximal primary angioplasty. METHODS: This is a retrospective analysis of consecutive patients in a single center who underwent submaximal primary angioplasty between January 1, 2012 and December 31, 2015. The peri-procedural complications and long-term outcomes are reported. RESULTS: Primary angioplasty was successfully performed in 129 patients (97.0%). The mean degree of pre-procedural stenosis was 81.9 ± 10.2%, and the degree of residual stenosis was 40.7 ± 19.1%. There were nine (6.8%) peri-procedural complications within 30 days, including seven ischemic strokes, one subarachnoid hemorrhage, and one asymptomatic intracerebral hemorrhage. None of them resulted in death. One-year follow-up was available in 122 patients (91.7%). Three more ischemic strokes (2.3%) which were in the territory of the treated artery occurred between 30 days and 1 year. The 1-year stroke and death rate was 9.0%, including peri-procedural stroke. Kaplan-Meier analysis showed a 3-year stroke-free survival of 87.2%. CONCLUSION: Submaximal primary angioplasty can be performed with a low peri-procedural complication rate and relatively good clinical outcome at long-term follow-up for symptomatic ICAS patients.

7.
Front Psychiatry ; 9: 455, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319462

RESUMO

Objective: This study aimed to investigate the association between cognitive impairment and cerebral haemodynamic changes in patients with chronic vertebra-basilar (VB) stenosis. Methods: Patients with severe posterior circulation VB stenosis and infarction or a history of infarction for more than 2 weeks from January 2014 to January 2015 were enrolled (n = 96). They were divided into three groups, namely, the computed tomography perfusion (CTP) normal group, the CTP compensated group, and the CTP decompensated group. Cognitive function was assessed using a validated Chinese version of the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Regression models were used to identify independent risk factors for cognitive impairment. Results: The MMSE and FAB scores of patients in the CTP decompensated group were significantly lower than those of patients in the CTP normal and CTP compensated groups (all p < 0.05). The RBANS total and its domain scores, including immediate memory, visual acuity, and delayed memory, in the CTP compensated and CTP decompensated groups were significantly lower than those in the CTP normal group (all p < 0.05). Multiple regression analyses showed that CTP compensation, CTP decompensation, severe VB tandem stenosis, and multiple infarctions were independent risk factors for cognitive impairment. Conclusions: Low perfusion caused by severe VB stenosis can lead to extensive cognitive impairments in areas such as immediate memory, visual span, and delayed memory.

8.
Neurochem Int ; 121: 140-145, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30291953

RESUMO

Subsequent inflammation in stroke plays an important role in the damage of neurons in the perilesional area. Therapeutic intervention targeting inflammation may be a promising complementary strategy to current treatments of stroke. Here, we explored the possible beneficial effects of tyrosol, a derivative of phenethyl alcohol and natural antioxidant, playing an anti-inflammatory role in astrocyte culture and in vitro oxygen glucose deprivation (OGD) model. MTT, western blot, ELISA and EMSA assays were carried out to investigate cell viability, protein expression level, cytokine expression and NF-κB activity. We found tyrosol protected cultured astrocytes against OGD-induced cell viability loss in MTT test. Meanwhile, tyrosol attenuated the released TNF-α and IL-6 level from astrocyte via regulating Janus N-terminal kinase (JNK). The reduction of cytokines from astrocyte might be due to its inhibition of astrocyte activation and regulation of STAT3 signaling pathway since tyrosol attenuated the expression level of GFAP (glial fibrillary acidic protein) and the phosphorylation of STAT3. Additionally, we demonstrated that tyrosol prevented the degradation of IκBα and the increase of IκBα phosphorylation in astrocytes exposed to OGD, which led to the suppression of NF-κB function during ischemia. Collectively, our results showed that tyrosol may be a promising complementary treatment compound for stroke via modulating the inflammatory response in astrocytes during ischemia.

9.
Stroke Vasc Neurol ; 3(3): 176-184, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30294474

RESUMO

Background and purpose: A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis (ICAS) combined with poor collaterals in China showed that the short-term safety and efficacy of stenting was acceptable. However, it remained uncertain whether the low event rate could be of a long term. We reported the 1-year outcome of this registry study to evaluate the long-term efficacy of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals. Methods: Patients with symptomatic ICAS caused by 70%-99% stenosis located at the intracranial internal carotid, middle cerebral, intracranial vertebral or basilar arteries combined with poor collaterals were enrolled. Balloon-mounted stent or balloon plus self-expanding stent were selected based on the ease of vascular access and lesion morphology determined by the operators. The primary outcome was the rate of 30-day stroke, transient ischaemic attack and death, and 12-month ischaemic stroke within the same vascular territory, haemorrhagic stroke and vascular death after stenting. Results: From September 2013 to January 2015, 300 patients (ages 58.3±9.78 years) were recruited. Among them, 159 patients were treated with balloon-mounted stent and 141 with balloon plus self-expanding stent. During the 1-year follow-up, 25 patients had a primary end point event. The probability of primary outcome at 1 year was 8.1% (95% CI 5.3% to 11.7%). In 76 patients with digital subtraction angiography follow-up, 27.6% (21/76) had re-stenosis ≥50% and 18.4% (14/76) had re-stenosis ≥70%. No baseline characteristic was associated with the primary outcome. Conclusion: The event rate remains low over 1 year of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals. Further randomised trial of comparing individually tailored stenting with best medical therapy is needed. Trial registration number: NCT01968122; Results.

10.
World Neurosurg ; 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30244073

RESUMO

OBJECTIVE: To estimate the association of different etiologies of cardioembolism (CE), intracranial arterial stenosis (ICAS), or the combination of these conditions with outcomes of mechanical thrombectomy in acute ischemic stroke. METHODS: Data from the intervention group of the Endovascular therapy for Acute ischemic Stroke Trial (EAST) were analyzed. In 140 patients, the presence of CE, ICAS, neither CE nor ICAS, or both conditions was assessed. The primary outcome was a favorable outcome at 90 days (modified Rankin Scale score 0-2); secondary outcomes included successful reperfusion (modified Thrombolysis In Cerebral Infarction grade 2b-3), symptomatic intracerebral hemorrhage, and 90-day mortality. RESULTS: Of 140 patients, 47 had neither CE nor ICAS, 35 had ICAS but not CE, 46 had CE but not ICAS, and 12 had both CE and ICAS. The rate of favorable outcome was 67.1% in the no CE and no ICAS group, 74.3% in the ICAS without CE group, 41.3% in the CE without ICAS group, and 33.3% in the CE and ICAS group. The CE and ICAS group had poor outcomes (odds ratio = 0.20 after adjusting for age, sex, and National Institutes of Health Stroke Scale score; 95% confidence interval, 0.04-0.95; P = 0.043). No significant differences were observed in secondary outcomes. CONCLUSIONS: The presence of both CE and ICAS was associated with poor outcome in patients with anterior circulation large-vessel occlusion treated with endovascular thrombectomy. Future studies are warranted to further explore this association.

11.
J Stroke Cerebrovasc Dis ; 27(10): 2822-2828, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30072180

RESUMO

BACKGROUND: The diffusion-weighted imaging (DWI) brain stem score (BSS) is an easy to use and can predict the clinical outcome of acute basilar artery occlusion (BAO) who underwent endovascular thrombectomy. The purpose of the current study was to validate its performance in Chinese acute BAO patients treated with mechanical thrombectomy. METHODS: Fifty consecutive patients with acute BAO who received early magnetic resonance imaging and treated with mechanical thrombectomy in a single-center were included. Early ischemic damage on DWI was evaluated by applying BSS system. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the score system and multivariate logistic regression analysis was performed to identify predictor of clinical outcome. RESULTS: Favorable outcomes were achieved in 38% patients (19 of 50 patients). Recanalization was successful in 92% patients (46 of 50 patients). Mortality rate was 26% (n = 13/50). In ROC curve analysis, the area under ROC curve of BSS .864 (95% confidence interval [CI], .738-.945) to predict favorable and .769 (95% CI, .628-.877) to predictor mortality. In logistic regression adjusted for age, baseline National Institute of Health Stroke Scale and time to puncture, DWI BSS ≤2 (odds ratio [OR], 12.416; 95% CI, 2.520-61.179; P = .002) and DWI BSS >3 (OR, 7.871; 95% CI, 1.353-45.797; P = .022) were the independent predictor for favorable outcome and mortality at 3 months respectively. CONCLUSIONS: The results of this study suggest that the DWI BSS can be used to predict clinical outcome in patients with acute BAO treated with mechanical thrombectomy at 3 months.


Assuntos
Tronco Encefálico/irrigação sanguínea , Tronco Encefálico/diagnóstico por imagem , Técnicas de Apoio para a Decisão , Imagem de Difusão por Ressonância Magnética , Trombectomia/métodos , Insuficiência Vertebrobasilar/terapia , Idoso , Angiografia Digital , Área Sob a Curva , Tronco Encefálico/fisiopatologia , Angiografia Cerebral/métodos , Circulação Cerebrovascular , Distribuição de Qui-Quadrado , China , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Trombectomia/efeitos adversos , Trombectomia/mortalidade , Fatores de Tempo , Resultado do Tratamento , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/mortalidade , Insuficiência Vertebrobasilar/fisiopatologia
12.
Stroke Vasc Neurol ; 3(1): 17-21, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29600003

RESUMO

Background: The outcome of acute ischaemic stroke due to tandem vertebrobasilar artery occlusion was poor. Endovascular revascularisation may be a positive approach for acute basilar artery occlusion combined with vertebral ostium stenosis or occlusion. We reported seven patients with acute vertebrobasilar tandem occlusion by using angioplasty or stenting for proximal lesion and thrombectomy for distal occlusion. Materials and methods: Consecutive patients with acute tandem vertebrobasilar artery occlusion at two centres were included in this study. We retrospectively analysed the clinical, technical and functional outcomes of the patients. Results: From March 2016 to March 2017, seven patients were included. The mean age and National Institute of Health Stroke Scale score at admission was 57 years and 22, respectively. A reverse approach was used in five patients. The Thrombolysis in Cerebral Infarction score 2b-3 was acquired in all patients. There were no procedural complications. The modified Rankin Scale score was 1-2 for three patients and 4 for one patient at 3 months. Three patients died at 3 months of follow-up. Conclusions: Endovascular revascularisation may be feasible for acute tandem vertebrobasilar artery occlusion, and more researches are needed.

13.
J Stroke Cerebrovasc Dis ; 27(6): 1570-1574, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29422378

RESUMO

BACKGROUND: Recently, the Basilar Artery on Computed Tomography Angiography (BATMAN) score predicts clinical outcome of acute basilar artery occlusion (BAO), yet there is no extensive external validation. The purpose of this study was to validate the prognostic value of BATMAN scoring system for the prediction of clinical outcome in patients with acute BAO treated with endovascular mechanical thrombectomy by using cerebral digital subtraction angiography (DSA). METHODS: We analyzed the clinical and angiographic data of consecutive patients with acute BAO from March 2012 to November 2016. The BATMAN scoring system was used to assess the collateral status and thrombus burden. Thrombolysis in Cerebral Infarction (TICI) score 2b-3 was defined as successful recanalization. Receiver operating characteristic (ROC) curve was used to determine the area under the curve (AUC) and the optimum cutoff value. Multivariate regression analysis was used to identify the predictor of clinical outcome. RESULTS: This study included 63 patients with acute BAO who underwent mechanical thrombectomy. Of these patients, 90.5% (57/63) achieved successful recanalization (TICI, 2b-3) and 34.9% (22/63) had a favorable outcome (modified Rankin Scale score 0-2). ROC analysis indicated that the AUC of the BATMAN score was .722 (95% confidence interval [CI], .594-.827), and the optimal cutoff value was 3 (sensitivity = 72.73, specificity = 63.41). In multivariate logistic regression analysis, the BATMAN score higher than 3 was associated with favorable outcome (odds ratio, 5.214; 95% CI, 1.47-18.483; P = .011). CONCLUSIONS: The BATMAN score on DSA seems to predict the functional outcome in patients of acute BAO treated with mechanical thrombectomy.


Assuntos
Angiografia Digital , Artéria Basilar/diagnóstico por imagem , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/métodos , Trombectomia/métodos , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/terapia , Idoso , Área Sob a Curva , Artéria Basilar/fisiopatologia , Circulação Cerebrovascular , Distribuição de Qui-Quadrado , Circulação Colateral , Avaliação da Deficiência , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Trombectomia/efeitos adversos , Resultado do Tratamento , Insuficiência Vertebrobasilar/fisiopatologia
14.
CNS Neurosci Ther ; 24(2): 154-161, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29293287

RESUMO

AIMS: To evaluate whether visual field impairment (VFI) can predict stroke recurrence in patients with vertebral-basilar (VB) stroke. METHODS: A total of 326 patients were eligible for a VFI evaluation within 1 week of stroke onset. One-year follow-up data were obtained after VB stroke and other vascular events. All predictors were determined using Cox regression models. RESULTS: The overall incidence of recurrent VB stroke and transient ischemic attack (TIA) was 29% (n = 92). After multivariate adjustment, severe and moderate VFI were predictors of recurrent VB stroke and TIA. CONCLUSIONS: VFI is an independent predictor of recurrent VB stroke and TIA.

15.
Neuroreport ; 29(2): 92-98, 2018 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-29120942

RESUMO

ß-Amyloid (Aß)-induced neuronal toxicity is an early event in the pathogenesis of Alzheimer's disease. Quetiapine (QTP) is an atypical antipsychotic drug that has neuroprotectant properties, but little is known about its direct protective effects on neurons against the Aß-induced cell toxicity. In the present study, we investigated the neuroprotective effects of QTP on Aß25-35-induced cell death and the possible underlying mechanisms in primary cultures of neurons. Exposure of cortical neurons to 10 µM or more Aß25-35 caused significant viability loss in a MTT assay, and the toxic effects were not significantly prevented by the simultaneous coadministration of QTP. However, pretreated astrocyte conditioned medium (ACM) with QTP (ACMQTP) for 24 h markedly protected the neurons against the amyloid-induced cell loss. Furthermore, we revealed that QTP increased both the release of brain-derived neurotrophic factor from cultured astrocytes and the phosphorylation of extracellular signal-regulated kinase after 24 h of treatment, which might be responsible for its protective effects on neurons. Consistent with the aforementioned findings, the protective effects of ACM on neurons could potentially be abolished by the extracellular signal-regulated kinase inhibitor and tropomyosin receptor kinase B receptor blocker. In conclusion, our data demonstrated that QTP exerted its neuroprotective effects against amyloid toxicity by enhancing the brain-derived neurotrophic factor release from astrocytes.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Astrócitos/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/toxicidade , Fumarato de Quetiapina/farmacologia , Peptídeos beta-Amiloides/metabolismo , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Morte Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Técnicas de Cocultura , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Camundongos Endogâmicos ICR , Neurônios/metabolismo , Neurônios/patologia , Fragmentos de Peptídeos/metabolismo , Fosforilação/efeitos dos fármacos , Receptor trkB/antagonistas & inibidores , Receptor trkB/metabolismo
16.
J Neurointerv Surg ; 10(8): 746-750, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29203731

RESUMO

OBJECTIVE: To investigate the safety and efficacy of mechanical thrombectomy plus rescue therapy for intracranial large artery occlusion (ILAO) with underlying intracranial atherosclerosis (ICAS). METHODS: Patients enrolled in the intervention group of EAST (Endovascular Therapy for Acute ischemic Stroke Trial) were analyzed. For underlying ICAS identified during the stent retrieval procedure, rescue treatment was required for those with (1) a degree of arterial stenosis >70% or (2) any degree of arterial with blood flow impairment or (3) evidence of re-occlusion. Outcomes were compared between the ICAS group and the embolic group. Multivariate logistic regression was performed to determine independent predictors of functional independence at 90 days. RESULTS: Among the 140 patients included in the analysis, underlying ICAS was identified in 47 (34%), and 30 patients (21.4%) were considered to be eligible to receive rescue treatment. Of the 30 patients, 27 (90%) actually received rescue therapy. Recanalization rate (95.7% vs 96.8%, P=0.757) and functional independence at 90 days (63.8% vs 51.6%, P=0.169) were comparable between the ICAS group and the embolic group. No significant difference in symptomatic hemorrhage (4.3% vs 4.3%, P=1.000) or death (12.8% vs 12.9%, P=0.982) was found between the two groups. National Institutes of Health Stroke Scale score at presentation (OR=0.865, 95% CI 0.795 to 0.941; P=0.001) and modified Thrombolysis in Cerebral Infarction after the procedure (OR=2.864, 95% CI 1.018 to 8.061; P=0.046) were independently associated with functional independence at 90 days. CONCLUSIONS: Mechanical thrombectomy is safe in patients with ILAO with underlying ICAS. By employing a standard rescue therapy, favorable outcomes could be achieved in such patients. CLINICAL TRIAL REGISTRATION: NCT02350283 (Post-results).


Assuntos
Isquemia Encefálica/terapia , Transtornos Cerebrovasculares/terapia , Procedimentos Endovasculares/métodos , Arteriosclerose Intracraniana/terapia , Acidente Vascular Cerebral/terapia , Trombectomia/métodos , Idoso , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/epidemiologia , Estudos de Coortes , Feminino , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Stents , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento
17.
World Neurosurg ; 109: e318-e328, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28987852

RESUMO

BACKGROUND AND OBJECTIVE: Early recanalization of acute posterior circulation stroke caused by large intracranial vessel occlusion by mechanical thrombectomy with stent retrievers may improve the outcome of patients. However, evidence of patient selection is still lacking. This study investigated the prognostic factors of acute posterior circulation stroke caused by large intracranial arterial occlusion when treated with stent-retriever thrombectomy. METHODS: A total of 69 patients from March 2012 to November 2016 were included in the study. These patients presented with acute posterior circulation stroke caused by large intracranial vessel occlusion and underwent mechanical thrombectomy with Solitaire AB or combined with additional balloon and/or stenting angioplasty. Baseline characteristics, clinical course, and imaging data of the patients were analyzed. Good clinical outcome (defined as a modified Rankin Scale score of 0-2 at 90 days) and safety outcome (defined as death within 90 days after thrombectomy) were considered as end points. The association between factors with good clinical outcome and safety outcome was evaluated with both logistic regression and receiver operating characteristic curve analyses. RESULTS: Of the 69 patients, mean age was 59 years (standard deviation, 8 years) and men comprised 82.6% (57/69). The median onset-to-treatment time was 360 minutes (interquartile range, 250-537 minutes). The median National Institutes of Health Stroke Scale (NIHSS) score was 25 (interquartile range, 17-30) on admission. Successful recanalization was achieved in 62 of the 69 cases (89.9%) and 36.2% (25/69) were independent at 90 days. Regression analysis showed that stroke subtype (intracranial atherosclerotic disease vs. embolism; odds ratio [OR], 0.101; 95% confidence interval [CI], 0.020-0.501; P = 0.005), baseline NIHSS score (≥22 vs. <22; OR, 0.157; 95% CI, 0.040-0.614; P = 0.008) and posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) on diffusion-weighted imaging [DWI] (weighted magnetic resonance imaging) before thrombectomy (≥6 vs. <6; OR, 7.335; 95% CI, 1.495-36.191; P = 0.014) were independent predictive factors of good clinical outcome, respectively at 90 days, whereas high NIHSS score (≥30 vs. <30; OR, 5.569; 95% CI, 1.573-19.716; P = 0.008) and collateral status (≥2 vs. <2; OR, 0.210; 95% CI, 0.059-0.752; P = 0.016) before treatment were associated with mortality at 90 days. Based on receiver operating characteristic curves, baseline NIHSS score (area under the curve [AUC] = 0.779; cutoff, ≥22; P < 0.001; sensitivity, 72%; specificity, 77.3%), pc-ASPECTS on DWI (AUC = 0.820; cutoff, ≥6; P < 0.001; sensitivity, 72%; specificity, 77.3%) before treatment were independent indicators predicting good clinical outcome at 90 days. Increased risk of death by 90 days was associated with baseline NIHSS score (AUC = 0.719; cutoff, ≥30; P = 0.007; sensitivity, 64.7%; specificity, 78.9%) and worse collateral status (AUC = 0.820; cutoff, ≥2; P < 0.001; sensitivity, 58.8%; specificity, 80.8%) before treatment. CONCLUSIONS: Stroke subtype, initial stroke severity, and pc-ASPECTS on DWI as well as collateral status before thrombectomy are independent factors affecting the clinical outcome in patients treated with Solitaire AB thrombectomy for acute posterior circulation stroke caused by large intracranial vessel occlusion.


Assuntos
Angioplastia , Stents , Acidente Vascular Cerebral/cirurgia , Trombectomia , Insuficiência Vertebrobasilar/cirurgia , Idoso , Angioplastia com Balão , Área Sob a Curva , Angiografia Cerebral , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Estudos Prospectivos , Curva ROC , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/fisiopatologia
18.
Int Heart J ; 58(5): 812-815, 2017 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-28966317

RESUMO

Paradoxical embolization is the mechanism for patent foramen ovale (PFO)-associated cryptogenic stroke and transcatheter closure of PFO may prevent recurrent ischemic stroke. Mechanical thrombectomy is promising to treat acute ischemic stroke due to high rates of reperfusion and reduced intracranial hemorrhage complications. We report the case of a 27-year-old woman with a massive cerebral infarction but no evidence for any atherosclerosis, who received an urgent mechanical thrombectomy with a Solitaire device. In order to ascertain the etiology of stroke, transcranial Doppler (TCD) and transesophageal echocardiograph (TEE) were conducted. TCD showed severe right-to-left shunting (shower effect) after Valsalva maneuver and bubble test and TEE identified a PFO. Therefore, the patient had suffered a paradoxical stroke associated with PFO. After two weeks of the stroke onset, transcatheter PFO closure with Cardio-O-Fix occluder was also performed successfully. During 1-year of follow-up, no recurrence of stroke occurred. Our case demonstrates that mechanical thrombectomy using a Solitaire device and transcatheter PFO closure can be safely and successfully performed to treat acute paradoxical stroke and prevent its recurrence.


Assuntos
Isquemia Encefálica/cirurgia , Embolia Paradoxal/cirurgia , Forame Oval Patente/cirurgia , Dispositivo para Oclusão Septal , Trombectomia/instrumentação , Adulto , Isquemia Encefálica/etiologia , Ecocardiografia Transesofagiana , Embolia Paradoxal/complicações , Feminino , Forame Oval Patente/complicações , Forame Oval Patente/diagnóstico , Humanos , Desenho de Prótese
19.
Stroke ; 48(3): 784-786, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28130545

RESUMO

BACKGROUND AND PURPOSE: We aimed to explore the risk factors of subacute thrombosis (SAT) after intracranial stenting for patients with symptomatic intracranial arterial stenosis. METHODS: From January to December 2013, all symptomatic intracranial arterial stenosis patients who underwent intracranial stenting in Beijing Tiantan Hospital were prospectively registered into this study. Baseline clinical features and operative data were compared in patients who developed SAT with those who did not. Binary logistic regression model was used to determine the risk factors associated with SAT. RESULTS: Of the 221 patients enrolled, 9 (4.1%) cases had SAT 2 to 8 days after stenting. Binary logistic analysis showed that SAT was related with tandem stenting (odds ratio [OR], 11.278; 95% confidence interval [CI], 2.422-52.519) and antiplatelet resistance (aspirin resistance: OR, 6.267; 95% CI, 1.574-24.952; clopidogrel resistance: OR, 15.526; 95% CI, 3.105-77.626; aspirin and clopidogrel resistance: OR, 12.246; 95% CI, 2.932-51.147; and aspirin or clopidogrel resistance: OR, 11.340; 95% CI, 2.282-56.344). CONCLUSIONS: Tandem stenting and antiplatelet resistance might contribute to the development of SAT after intracranial stenting in patients with symptomatic intracranial arterial stenosis.


Assuntos
Constrição Patológica/terapia , Stents/efeitos adversos , Trombose/tratamento farmacológico , Adulto , Idoso , Aspirina/uso terapêutico , Clopidogrel , Feminino , Humanos , Ataque Isquêmico Transitório , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Fatores de Risco , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico
20.
J Neurointerv Surg ; 9(2): 192-195, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26041100

RESUMO

BACKGROUND AND PURPOSE: Thrombelastography (TEG) is widely used for the measurement of platelet function. However, few studies have investigated the TEG parameters in patients receiving extracranial or intracranial artery stenting for ischemic cerebrovascular disease. This study sought to describe the association of TEG parameters before the procedure with post-procedural ischemic events after extracranial or intracranial artery stenting. METHODS: Patients in whom stenting was performed for extracranial or intracranial artery stenosis (70-99%) were recruited into the study. Blood samples were obtained for TEG to assess platelet function before stenting. The primary endpoint was ischemic stroke or transient ischemic attack in the territory of the stented artery. RESULTS: A total of 218 patients were included in the study. During a mean follow-up period of 132 days (range 98-226 days), 18 (8.3%) primary endpoint events were recorded. Compared with patients without ischemic events, the ADP-induced platelet-fibrin clot strength (MAADP) was significantly higher (41.57±15.10 vs 33.50±13.86, p=0.020) and the ADP inhibition rate (ADP%) was significantly lower in patients with ischemic events (39.54±23.15 vs 55.29±24.43, p=0.009). Multivariate analysis identified MAADP and ADP% as significant independent predictors of subsequent ischemic events with HRs of 1.036 and 0.965, respectively. From receiver operating characteristic curve analysis, MAADP >49.95 mm had the best predictive value of ischemic events. CONCLUSIONS: Our study suggests that TEG parameters MAADP and ADP% are associated with subsequent ischemic events in patients with extracranial or intracranial stents. CLINICAL TRIAL NUMBER: NCT01925872.


Assuntos
Isquemia Encefálica/diagnóstico , Stents/efeitos adversos , Tromboelastografia/métodos , Difosfato de Adenosina/farmacologia , Idoso , Estudos de Coortes , Constrição Patológica , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Ataque Isquêmico Transitório , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Testes de Função Plaquetária , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de Sobrevida , Tromboelastografia/normas
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