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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.
Stroke ; 50(3): 745-749, 2019 03.
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.

3.
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.

4.
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.

5.
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.

6.
J Int Med Res ; : 300060518799019, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30238823

RESUMO

Objective This study aimed to investigate the association between abnormal signs on susceptibility-weighted imaging (SWI) and post-treatment outcome in the early stage in patients with acute ischemic stroke. Methods Thirty-seven patients with middle cerebral artery territory infarction were recruited. Baseline and 24-hour follow-up magnetic resonance imaging was performed. Pre- and 24-hour post-treatment clinical conditions were assessed with the National Institutes of Health Stroke Scale (NIHSS) score. Prominent vessel sign (PVS) on SWI and infarcted areas on diffusion-weighted imaging (DWI) were assessed using the Alberta Stroke Program Early CT (ASPECT) score system. Susceptibility vessel sign (SVS) was evaluated and recorded. The associations between image abnormalities and clinical scores were analyzed. Results PVS was found in 35 patients and SVS in seven patients. The extent of PVS was significantly correlated with the post-treatment DWI ASPECT score (r = 0.79), but not with the post-treatment NIHSS score or the post-pre NIHSS difference score. The presence of SVS was significantly correlated with the post-treatment NIHSS score (r = 0.41). Conclusion PVS might be a useful predictor of early imaging prognosis and infarct growth in patients with acute ischemic stroke. SVS is related to a poor early outcome and could be useful for assessing stroke.

7.
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.

8.
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
9.
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
10.
Neurol Res ; 39(6): 498-503, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28436268

RESUMO

OBJECTIVES: Fractional flow reserve (FFR) accurately predicts the degree of stenosis and is now widely used to identify clinically significant severe coronary artery lesions. In the current study, we utilized a similar indicator, fractional flow (FF), to determine the hemodynamic impact of symptomatic intracranial atherosclerotic stenosis (ICAS) and to assess the correlation of FF with the severity of stenosis and collateral circulation. METHODS: Patients with symptomatic ICAS (70-99% stenosis) confirmed on digital subtraction angiography (DSA) were consecutively recruited. FF was obtained during DSA examination with the use of pressure sensors and was measured as a ratio, comparing measurements distal to an ICAS lesion (Pd) and within the aorta (Pa). The degree of leptomeningeal collateralization was graded from zero (absent) to four (complete compensatory). The correlation between FF, anatomical stenosis, and collateral status was then analyzed. RESULTS: Twenty-five patients with a mean age of 55.6 years were analyzed. The median percentage of stenosis and median FF were 82.3 and 0.68%, respectively. Eleven patients were found to have poor collateralization (grade 0-2), and fourteen patients were identified with good collateral circulation (grade 3-4). Overall, the hemodynamic impact of an atherosclerotic lesions worsened (decreased FF) as the percentage of stenosis increased, although this did not reach statistical significance (r = -0.398, p = 0.06). However, the status of collateralization significantly altered this correlation, worsening the hemodynamic impact in patients with poor collateral circulation (r = -0.677, p = 0.032). There was no difference in patients with good collateral circulation (r = -0.279, p = 0.356). CONCLUSION: An anatomically severe (70-99%) symptomatic ICAS lesion may generate significant hemodynamic stress downstream as assessed by the indicator FF, particularly in patients with poor collateral circulation. Further, good collateralization may mitigate this hemodynamic impact, partially explaining the protective effect of collateral circulation against recurrent stroke in such patients.


Assuntos
Circulação Cerebrovascular/fisiologia , Circulação Colateral/fisiologia , Constrição Patológica/fisiopatologia , Arteriosclerose Intracraniana/etiologia , Estresse Fisiológico , Angiografia Digital/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Fisiológico/fisiologia
11.
Interv Neuroradiol ; 23(3): 267-273, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28335662

RESUMO

Background The purpose of this study was to determine the performance of computed tomography angiography (CTA) by using a scoring system to predict anterograde and collateral blood flow status in patients with symptomatic middle cerebral artery (MCA) stenosis with use of conventional angiography as standard reference. Methods We retrospectively identified all consecutive patients with unilateral symptomatic MCA stenosis in our center who underwent conventional angiography and CTA within 1 month. The anterograde and collateral blood flow (AnCo) scoring system consisted of anterograde score (AnS) and collateral score (CoS). Evaluation of the CTA images was done independently by two readers, based on the AnCo scoring system. The conventional angiography was assessed by using the Thrombolysis in Cerebral Infarction (TICI) and American Society of Interventional and Therapeutic Neuroradiology (ASITN/SIR) scoring system to determine the status of anterograde and collateral blood flow. Diagnostic performance of AnCo was evaluated by using the area under the receiver operating characteristic (ROC) curve. Results A total of 61 patients were included in the analysis with mean age of 53.4 ± 11.0 years. AnS demonstrated a strong correlation with TICI with statistical significance ( r = 0.786; p < 0.001). CoS had a modest yet statistically significant correlation with ASITN/SIR ( r = 0.574; p < 0.001). The ROC curve analysis for AnS demonstrated an area under the curve (AUC) of 0.894 ( p < 0.001) and the ROC curve analysis for CoS showed an AUC of 0.824 ( p < 0.001). Conclusions CTA was a potential method to evaluate anterograde and collateral blood flow status in patients with symptomatic unilateral MCA stenosis.


Assuntos
Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Arteriosclerose Intracraniana/diagnóstico por imagem , Circulação Colateral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
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
13.
J Cereb Blood Flow Metab ; 37(7): 2567-2576, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27702878

RESUMO

The fractional pressure ratio is introduced to quantitatively assess the hemodynamic significance of severe intracranial stenosis. A computational fluid dynamics-based method is proposed to non-invasively compute the FPRCFD and compared against fractional pressure ratio measured by an invasive technique. Eleven patients with severe intracranial stenosis considered for endovascular intervention were recruited and an invasive procedure was performed to measure the distal and the aortic pressure ( Pd and Pa). The fractional pressure ratio was calculated as [Formula: see text]. The computed tomography angiography was used to reconstruct three-dimensional (3D) arteries for each patient. Cerebral hemodynamics was then computed for the arteries using a mathematical model governed by Navier-Stokes equations and with the outflow conditions imposed by a model of distal resistance and compliance. The non-invasive [Formula: see text], [Formula: see text], and FPRCFD were then obtained from the computational fluid dynamics calculation using a 16-core parallel computer. The invasive and non-invasive parameters were tested by statistical analysis. For this group of patients, the computational fluid dynamics method achieved comparable results with the invasive measurements. The fractional pressure ratio and FPRCFD are very close and highly correlated, but not linearly proportional, with the percentage of stenosis. The proposed computational fluid dynamics method can potentially be useful in assessing the functional alteration of cerebral stenosis.


Assuntos
Pressão Sanguínea/fisiologia , Artérias Cerebrais/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Arteriosclerose Intracraniana/diagnóstico por imagem , Modelos Teóricos , Acidente Vascular Cerebral/diagnóstico por imagem , Aorta/fisiopatologia , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Circulação Cerebrovascular/fisiologia , Biologia Computacional , Constrição Patológica , Feminino , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/patologia , Arteriosclerose Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia
14.
Interv Neurol ; 5(1-2): 65-75, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27610123

RESUMO

PURPOSE: Current studies on endovascular intervention for intracranial atherosclerosis select patients based on luminal stenosis. Coronary studies demonstrated that fractional flow measurements assess ischemia better than anatomical stenosis and can guide patient selection for intervention. We similarly postulated that fractional flow can be used to assess ischemic stroke risk. METHODS: This was a feasibility study to assess the technical use and safety of applying a pressure guidewire to measure fractional flow across intracranial stenoses. Twenty patients with severe intracranial stenosis were recruited. The percentage of luminal stenosis, distal to proximal pressure ratios (fractional flow) and the fractional flow gradients across the stenosis were measured. Procedural success rate and safety outcomes were documented. RESULTS: All 20 patients had successful crossing of stenosis by the pressure guidewire. Ten patients underwent angioplasty, and 5 had stenting performed. There was one perforator stroke, but not related to the use of the pressure wire. For the 13 patients with complete pre- and postintervention data, the mean preintervention stenosis, fractional flow and translesional pressure gradient were 76.2%, 0.66 and 29.9 mm Hg, whilst the corresponding postintervention measurements were 24.7%, 0.88 and 10.9 mm Hg, respectively. Fractional flow (r = -0.530, p = 0.001) and the translesional pressure gradient (r = 0.501, p = 0.002) only had a modest correlation with the luminal stenosis. CONCLUSION: Fractional flow measurement by floating a pressure guidewire across the intracranial stenosis was technically feasible and safe in this study. Further studies are needed to validate its use for ischemic stroke risk assessment.

15.
Biomed Res Int ; 2016: 8380618, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27294139

RESUMO

The main causes of Alzheimer's disease remain elusive. Previous data have implicated the BACE-1 protein as a central player in the pathogenesis of Alzheimer's disease. However, many inhibitors of BACE-1 have failed during preclinical and clinical trials for AD treatment. Therefore, uncovering the exact role of BACE-1 in AD may have significant impact on the future development of therapeutic agents. Three- and six-month-old female APP/PS1 double transgenic mice were used to study abnormal accumulation of BACE-1 protein in brains of mice here. Immunofluorescence, immunohistochemistry, and western blot were performed to measure the distributing pattern and expression level of BACE-1. We found obvious BACE-1 protein accumulation in 3-month-old APP/PS1 mice, which had increased by the time of 6 months. Coimmunostaining results showed BACE-1 surrounded amyloid plaques in brain sections. The abnormal protein expression might not be attributable to the upregulation of BACE-1 protein, as no significant difference of protein expression was observed between wild-type and APP/PS1 mice. With antibodies against BACE-1 and CD31, we found a high immunoreactive density of BACE-1 protein on the outer layer of brain blood vessels. The aberrant distribution of BACE-1 in APP/PS1 mice suggests BACE-1 may be involved in the microvascular abnormality of AD.


Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Ácido Aspártico Endopeptidases/metabolismo , Encéfalo/metabolismo , Presenilina-1/genética , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/irrigação sanguínea , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Microvasos/metabolismo , Microvasos/patologia , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Presenilina-1/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
16.
PLoS One ; 11(2): e0148891, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26870959

RESUMO

BACKGROUND AND PURPOSE: Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non-responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes. METHODS: Patients with symptomatic extracranial or intracranial stenosis scheduled for stenting and receiving dual antiplatelets (clopidogrel 75 mg and aspirin 100 mg daily) for at least 5 days before intervention were enrolled. Ischemic events including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality within 12 months follow-up were recorded. We examined the influence of genetic polymorphisms on treatment outcome in our patients. RESULTS: A total of 268 patients were enrolled into our study and ischemic events were observed in 39 patients. For rs662 of paraoxonase 1 (PON1), allele C was associated with an increased risk of ischemic events (OR = 1.64, 95%CI = 1.03-2.62, P = 0.029). The A-allele carriers of rs2046934 of P2Y12 had a significant association with adverse events (OR = 2.01, 95%CI = 1.10-3.67, P = 0.041). The variant T-allele of cyclooxygenase-1 (COX1) rs1330344 significantly increased the risk of recurrent clinical events (OR = 1.85, 95%CI = 1.12-3.03, P = 0.017). The other single nucleotide polymorphism (SNP) had no association with ischemic events. CONCLUSIONS: PON1, P2Y12 and COX1 polymorphisms were associated with poorer vascular outcomes. Testing for these polymorphisms may be valuable in the identification of patients at risk for recurrent ischemic events.


Assuntos
Arildialquilfosfatase/genética , Isquemia Encefálica/genética , Ciclo-Oxigenase 1/genética , Receptores Purinérgicos P2Y12/genética , Idoso , Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Recidiva , Stents
17.
World Neurosurg ; 89: 301-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26875658

RESUMO

OBJECTIVE: To determine the safety and efficacy of endovascular treatment with the Solitaire device for acute basilar artery occlusion (ABAO) and identify factors affecting clinical outcomes. METHODS: We enrolled 36 consecutive ABAO patients (aged 58.6 ± 8.10 years) who underwent mechanical thrombectomy with the Solitaire device. We analyzed baseline characteristics, mechanical thrombectomy results, and factors predicting clinical outcomes, which were assessed at 90 days. RESULTS: The median prethrombectomy National Institutes of Health Stroke Scale (NIHSS) score was 25.50 (interquartile range: 21.00-29.00); the median prethrombectomy Glasgow Coma Scale (GCS) score was 8.00 (5.00-9.75). Thirty patients (83.3%) had atherosclerotic stenosis of the occluded artery, and 25 underwent angioplasty (69.4%). Recanalization was successful (Thrombolysis in Cerebral Infarction grade: 2b-3) in 34 patients (94.4%). Six symptomatic intracranial hemorrhages (16.67%) occurred. Favorable outcomes (modified Rankin scale [mRS] score: 0-2) were achieved in 27.8% patients (10/36). The overall mortality rate was 30.6% (11/36) at 90 days. On univariate analysis, low prethrombectomy GCS and high post-thrombectomy NIHSS scores were associated with poor outcomes (mRS score >2) and mortality. Prethrombectomy unconsciousness, onset-to-recanalization time > 10.5 hours, and severe stenosis were associated with poor outcomes. Age ≥ 60 years was associated with mortality. CONCLUSIONS: Endovascular treatment with the Solitaire device yielded high recanalization rates in ABAO patients and favorable clinical outcomes in approximately one third of patients. Intracranial stenosis was the main cause of occlusion. Angioplasty was commonly performed during mechanical thrombectomy to improve recanalization and prognosis. Early recanalization and better prethrombectomy status predicted better outcomes.


Assuntos
Arteriopatias Oclusivas/cirurgia , Artéria Basilar/cirurgia , Procedimentos Endovasculares/instrumentação , Trombectomia/instrumentação , Insuficiência Vertebrobasilar/cirurgia , Doença Aguda , Arteriopatias Oclusivas/mortalidade , Procedimentos Endovasculares/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/mortalidade , Placa Aterosclerótica/cirurgia , Estudos Prospectivos , Índice de Gravidade de Doença , Trombectomia/métodos , Resultado do Tratamento , Insuficiência Vertebrobasilar/mortalidade
18.
J Neurointerv Surg ; 7(5): 331-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24759694

RESUMO

BACKGROUND AND PURPOSE: High periprocedural complication rate is a key limitation of endovascular treatment of intracranial atherosclerotic disease (ICAD), despite potential risk reduction of recurrent stroke. Taking lessons from the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Arterial Stenosis (SAMMPRIS) trial, targeting a selected patient population, we prospectively evaluated the feasibility and safety of tailored angioplasty and/or stenting for patients with ICAD. METHODS: From November 2011 to October 2012, 158 patients with symptomatic ICAD caused by hypoperfusion combined with poor collateral flow were consecutively recruited into a prospective single center study. Patients were divided into three groups based on arterial access and lesion morphology: balloon mounted stent group (group BS) for smooth access and Mori A lesion, angioplasty plus self-expanding stent group (group AS) for tortuous access and Mori B or C lesion, and angioplasty group (group AG) for tortuous access and Mori A lesion. The primary endpoints were successful procedure rate and any vascular event within 30 days. RESULTS: Overall technical success rate was 96.3% (154/158). There were significant differences in the technical success rate: 89.7% (35/39) in group AG compared with 97.5% (79/81) in group BS and 100% (38/38) in group AS (p=0.042). The 30 day composite stroke, myocardial infarction, or death rate was 4.4% (7/158). Stroke within 30 days occurred in four patients in group BS and in three patients in group AS. CONCLUSIONS: Individualized treatment of ICAD using tailored devices according to arterial access and lesion morphology was feasible and safe in symptomatic patients caused by hypoperfusion with poor collateral flow.


Assuntos
Angioplastia/métodos , Arteriosclerose Intracraniana/terapia , Avaliação de Resultados (Cuidados de Saúde)/estatística & dados numéricos , Stents , Acidente Vascular Cerebral , Adulto , Idoso , Angioplastia/efeitos adversos , Angioplastia/instrumentação , Angioplastia/estatística & dados numéricos , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Angioplastia com Balão/métodos , Angioplastia com Balão/estatística & dados numéricos , Ensaios Clínicos como Assunto , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Arteriosclerose Intracraniana/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Stents/efeitos adversos , Stents/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia
19.
J Neurointerv Surg ; 7(12): 888-91, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25332411

RESUMO

BACKGROUND AND PURPOSE: The long term results of vertebral artery ostium (VAO) stenting remain uncertain. We sought to evaluate the incidence and risk factors for recurrent ischemic events on long term follow-up in patients who have undergone VAO stenting. METHODS: 190 consecutive patients who had undergone a total of 202 stenting procedures for symptomatic atherosclerotic VAO stenosis between January 2011 and December 2012 were screened. Baseline demographics of the patients and morphological features of VAO were recorded. The primary outcome events analyzed included recurrent transient ischemic attack (TIA), stroke, and vascular related mortality. Risk factors for these recurrent events were identified. Other outcome events analyzed included in-stent restenosis (ISR) ≥50% and stent fracture noted on follow-up. RESULTS: Of the 188 patients with available follow-up data (mean follow-up period 16.7 months), 34 patients suffered recurrent TIAs (18.1%); none had stroke or death. 40 patients were found to have ISR (21.2%) and nine patients had stent fracture (4.7%). Patients with recurrent events were significantly more likely to have ISR, stent fracture, vessel tortuosity, and hyperlipidemia than patients without recurrent events. CONCLUSIONS: Stenting for VAO stenosis seems to be safe and efficacious. The majority of recurrent events were TIAs, which may be related to ISR, stent fracture, vessel tortuosity, and hyperlipidemia.


Assuntos
Procedimentos Endovasculares/tendências , Stents/tendências , Insuficiência Vertebrobasilar/diagnóstico , Insuficiência Vertebrobasilar/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
20.
J Neurointerv Surg ; 7(2): 131-4, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24443411

RESUMO

BACKGROUND AND PURPOSE: In a swine stroke model we have previously demonstrated a high-intensity fluid attenuated inversion recovery (FLAIR) signal representing the erythrocyte component of the clot. We hypothesized that the intensity of the FLAIR clot signal in patients with acute stroke may predict the efficacy of recanalization by thrombectomy devices. In this study we compared the pretreatment FLAIR signal intensity of the clots in the distal internal carotid artery (ICA) and the degree of angiographic recanalization rate after mechanical thrombectomy. METHODS: 25 consecutive acute stroke patients with ICA terminus (ICA-T) occlusion diagnosed with MRI at the UCLA Medical Center between 2002 and 2013 were retrospectively reviewed. The intensity of the FLAIR clot signal at the distal ICA was blindly compared with the angiographic recanalization status (successful recanalization defined as Thrombolysis In Cerebral Infarction (TICI) score of 2b-3) and non-successful recanalization as TICI score 0-2a) after endovascular treatment. Multivariate logistic regression analysis for successful recanalization was performed. RESULTS: Successful recanalization was achieved in 40% of patients (10/25) and showed a significantly higher FLAIR intensity (p=0.014). The cut-off value for clot intensity on the FLAIR sequence to predict recanalization was 0.7952, with 70% sensitivity and 80% specificity (95% CI 0.59 to 0.96) using a receiver operating characteristic curve. In multivariate logistic regression analysis, only a high FLAIR clot intensity (>0.7952) was associated with successful recanalization (OR 16.79; 95% CI 1.29 to 218.92; p=0.031). CONCLUSIONS: High signal intensity on FLAIR clot imaging may predict successful recanalization after endovascular therapy for ICA-T occlusion.


Assuntos
Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Revascularização Cerebral/métodos , Procedimentos Endovasculares/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
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