Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.195
Filtrar
1.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(8. Vyp. 2): 49-57, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33016677

RESUMO

AIM: To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS) across age groups according to the World Health Organization classification. MATERIAL AND METHODS: The study is an additional analysis across age groups among patients participated in the randomized double blind multicenter placebo-controlled, in parallel groups trial EPICA. All subjects (62 men and 88 women) were subdivided into age groups: younger than 60 years, 60-65 years, 76-90 years. Additionally, all participants were divided into 2 populations: ITT (Intent to treat population, patients who received at least one treatment/placebo dose) and PP (Per protocol population, patients who received treatment per study protocol). Results of Modified Rankin scale (mRs) at the end of treatment period, Barthel index, Beck depression inventory, European Quality of Life Questionnaire were assessed. RESULTS: The efficacy of mexidol assessed with all the scales did not differ depending on the age group. By the end of treatment, the mean mRS score was lower in the 76-90 years subgroup (in both populations), compared to placebo (p<0.001). The decrease in mean mRS score (Visit 1-5) was more prominent in patients aged 60-65 years (p=0.025), including patients with diabetes mellitus (DM). Patients aged 76-90 years and patients with DM, compared to placebo, had a decrease of the severity of cognitive-affective depression symptoms (p=0.049 and p=0.02) and an increase in patients without problems with everyday activities (p=0.007 and p=0.02). Patients with DM, compared to placebo, also had the higher levels of everyday activity (p=0.023) and quality of life (p=0.045). There were no statistically significant differences in the frequency of side-effects in patients of all groups. CONCLUSION: It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages in all age groups, including patients with DM.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Picolinas/efeitos adversos , Picolinas/uso terapêutico , Qualidade de Vida
2.
Nat Commun ; 11(1): 4078, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843630

RESUMO

Acute stroke causes complex, pathological, and systemic responses that have not been treatable by any single medication. In this study, using a murine transient middle cerebral artery occlusion stroke model, a novel therapeutic strategy is proposed, where blood replacement (BR) robustly reduces infarctions and improves neurological deficits in mice. Our analyses of immune cell subsets suggest that BR therapy substantially decreases neutrophils in blood following a stroke. Electrochemiluminescence detection demonstrates that BR therapy reduces cytokine storm in plasma and ELISA demonstrates reduced levels of matrix metalloproteinase-9 (MMP-9) in the plasma and brains at different time points post-stroke. Further, we have demonstrated that the addition of MMP-9 to the blood diminishes the protective effect of the BR therapy. Our study is the first to show that BR therapy leads to profoundly improved stroke outcomes in mice and that the improved outcomes are mediated via MMP-9. These results offer new insights into the mechanisms of stroke damage.


Assuntos
Substitutos Sanguíneos/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Encéfalo/metabolismo , Animais , Encéfalo/patologia , Infarto Encefálico/tratamento farmacológico , Isquemia Encefálica/patologia , Morte Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/complicações , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia
3.
J Pharmacol Sci ; 144(2): 69-75, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32713799

RESUMO

The mechanism of the papaverine (PV) for the treatment of cerebral ischemia remains unclear. A total of 42 mice induced with focal cerebral ischemia were randomly divided into three groups: PV,baicalin (BA)and vehicle group. Both PV and BA could significantly reduce the ischemic infarct volume (P < 0.05). Pathway enrichment analysis was performed on MetaCore™ to search the molecular pathways associated with the gene expression profile of PV, compared with vehicle and BA. Compared with vehicle, we found that 60% of the top 10 pathways in PV group were related to immune response. The top 10 biological processes of the targeted pathways were mainly related to the multiple immunomodulatory process of neuro-vascular inflammation, including immune_Th17-deried cytokins, regulation of angiogenesis, cell adhesion_Leucocyte chemotaxis, antigen presentation, cell adhesion_synaptic contact, and inflammation related to Amphoterin signaling. Moreover, compared with BA, 17 pathways of PV were identified, and 58.82% (10/17) were also related to immune response, especially, half of the top 10 pathways with the lower p-value. In these top 10 pathways, 4 were the cytokine-mediated signaling pathways, which play key role in inflammation, like IL-17 signaling pathways with the activation of G-CSF,IL-23,RANKL, p38MAPK and NF-κB.These findings indicate that PV may be an efficacious pluripotent anti-inflammatory agent against cerebral ischemic-reperfusion injury by targeting on multiple immunomodulatory process of neuro-vascular inflammation.


Assuntos
Anti-Inflamatórios , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Fatores Imunológicos , Papaverina/farmacologia , Papaverina/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Animais , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Inflamação , Interleucina-17/genética , Interleucina-17/metabolismo , Masculino , Camundongos Endogâmicos , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
4.
Artigo em Russo | MEDLINE | ID: mdl-32678563

RESUMO

Hyperlipidemia is the main risk factor for diseases caused by atherosclerosis including ischemic stroke. This publication provides practical recommendations and an algorithm for prescribing lipid-lowering therapy to post-ischemic stroke patients. The algorithm presents the steps for sequential administration of statins, ezetimibe, and PCSK9 inhibitors to achieve target levels of low-density lipoprotein cholesterol.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Anticolesterolemiantes , Isquemia Encefálica/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Pró-Proteína Convertase 9 , Acidente Vascular Cerebral/tratamento farmacológico
5.
Lancet ; 396(10244): 129-142, 2020 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-32653056

RESUMO

Stroke is a major cause of death and disability globally. Diagnosis depends on clinical features and brain imaging to differentiate between ischaemic stroke and intracerebral haemorrhage. Non-contrast CT can exclude haemorrhage, but the addition of CT perfusion imaging and angiography allows a positive diagnosis of ischaemic stroke versus mimics and can identify a large vessel occlusion target for endovascular thrombectomy. Management of ischaemic stroke has greatly advanced, with rapid reperfusion by use of intravenous thrombolysis and endovascular thrombectomy shown to reduce disability. These therapies can now be applied in selected patients who present late to medical care if there is imaging evidence of salvageable brain tissue. Both haemostatic agents and surgical interventions are investigational for intracerebral haemorrhage. Prevention of recurrent stroke requires an understanding of the mechanism of stroke to target interventions, such as carotid endarterectomy, anticoagulation for atrial fibrillation, and patent foramen ovale closure. However, interventions such as lowering blood pressure, smoking cessation, and lifestyle optimisation are common to all stroke subtypes.


Assuntos
Encéfalo/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Amilose/uso terapêutico , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/prevenção & controle , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/cirurgia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/fisiopatologia , Hemorragia Cerebral/cirurgia , Angiografia por Tomografia Computadorizada/métodos , Intervenção Médica Precoce/métodos , Endarterectomia das Carótidas/métodos , Procedimentos Endovasculares/métodos , Forame Oval Patente/cirurgia , Humanos , Pessoa de Meia-Idade , Seleção de Pacientes , Imagem de Perfusão/métodos , Polímeros/uso terapêutico , Recidiva , Acidente Vascular Cerebral/epidemiologia , Succinatos/uso terapêutico , Trombectomia/métodos , Terapia Trombolítica/métodos , Tomografia Computadorizada por Raios X/métodos
6.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3063-3072, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726012

RESUMO

Ginkgo biloba and Panax notoginseng are both herb medicines for cerebrovascular disease, and play an active role in treating ischemic cerebrovascular disease(ICVD). Their mechanisms of action include antioxidant stress, nerve protection, vascular protection. According to the comparative study of literatures, G. biloba has a certain protective effect from the early stage of free radical formation throughout the whole process of causing cell inflammation and apoptosis in antioxidant stress; while P. notoginseng has mainly anti-inflammatory, anti-apoptosis effects. In the nerve protection and repair of nerve damage caused by glutamate, both could promote neurogenesis, repair damaged axons and protect nerve cells. In addition, G. biloba could also relieve neurotoxicity caused by glutamate damage, while P. notoginseng have a unique effect in repairing blood-brain barrier(BBB) and blood vessel regeneration. In clinic, they are used as auxiliary drugs in combination with thrombolytic therapy, and play curative effects in alleviating inflammation, eliminating edema, improving the cure rate and the prognosis. For cerebral diseases caused by chronic cerebral hypoperfusion, G. biloba could reduce inflammation and improve cognition. In addition, G. biloba could protect neurocyte by adjusting the secretion of dopamine in vivo, and has a certain effect on antidepressant diseases, which however needs further studies.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Panax notoginseng , Plantas Medicinais , Ginkgo biloba , Humanos , Fitoterapia , Extratos Vegetais/uso terapêutico
7.
Neurol Sci ; 41(9): 2325-2329, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32656711

RESUMO

The sudden worldwide outbreak of Coronavirus Disease 2019 (COVID-19) has certainly provided new challenges in the management of acute ischaemic stroke, and the risk-benefit ratio of intravenous thrombolysis in COVID-19 positive patients is not well known. We describe four COVID-19 patients treated with intravenous thrombolysis for acute ischaemic stroke. Although rt-PA administration is the main therapeutic strategy, our patients experienced unpredictable complications and showed atypical features: the overall mortality was very high. In conclusion, in this article, we provide information about these cases and discuss the possible explanation behind this trend.


Assuntos
Betacoronavirus , Isquemia Encefálica/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Proteínas Recombinantes/administração & dosagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem
9.
BMC Neurol ; 20(1): 224, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493229

RESUMO

BACKGROUND: New evidence on the efficacy and safety of dual antiplatelet therapy for secondary stroke prevention have been realized in the recent years. An updated meta analysis was done to determine the effect of the various dual antiplatelets vs aspirin alone on recurrence rate of ischemic stroke, cardiovascular morbidity and mortality, and its safety profile as reported through major bleeding. METHODS: PubMed, Cochrane and Science Direct data bases were utilized, RCTs evaluating dual antiplatelet vs mono antiplatelet therapy for acute ischemic stroke or transient ischemic attack within < 72 h from ictus were searched up to July 2019. Risk ratio at 95% confidence intervals were calculated to evaluate stroke recurrence, cardiac events and mortality, and major bleeding. RESULTS: Sixteen randomized controlled trials with a population of 28, 032 patients were pooled into a meta-analysis. Dual antiplatelet therapy was significantly superior over mono antiplatelet therapy in the reduction of stroke (RR 0.75, 95% CI:0.68-0.83, p value< 0.00001) and composite events namely cardiovascular morbidity and mortality (0.73 95% CI: 0.65-0.82, p value < 0.00001), while bleeding events were noted to be not significant (1.22 95% CI: 0.87-1.70, p value = 0.25). CONCLUSION: In acute non-cardioembolic ischemic strokes or those who have suffered a transient ischemic attack, dual antiplatelet therapy was associated with efficacy in stroke recurrence and composite cardiac events, with a non-significant risk of major bleeding.


Assuntos
Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Aspirina/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Humanos , Ataque Isquêmico Transitório/epidemiologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/epidemiologia
10.
JAMA ; 323(21): 2170-2184, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32484532

RESUMO

Importance: Earlier administration of intravenous tissue plasminogen activator (tPA) in acute ischemic stroke is associated with reduced mortality by the time of hospital discharge and better functional outcomes at 3 months. However, it remains unclear whether shorter door-to-needle times translate into better long-term outcomes. Objective: To examine whether shorter door-to-needle times with intravenous tPA for acute ischemic stroke are associated with improved long-term outcomes. Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries aged 65 years or older who were treated for acute ischemic stroke with intravenous tPA within 4.5 hours from the time they were last known to be well at Get With The Guidelines-Stroke participating hospitals between January 1, 2006, and December 31, 2016, with 1-year follow-up through December 31, 2017. Exposures: Door-to-needle times for intravenous tPA. Main Outcomes and Measures: The primary outcomes were 1-year all-cause mortality, all-cause readmission, and the composite of all-cause mortality or readmission. Results: Among the 61 426 patients treated with tPA within 4.5 hours, the median age was 80 years and 43.5% were male. The median door-to-needle time was 65 minutes (interquartile range, 49-88 minutes). The 48 666 patients (79.2%) who were treated with tPA and had door-to-needle times of longer than 45 minutes, compared with those treated within 45 minutes, had significantly higher all-cause mortality (35.0% vs 30.8%, respectively; adjusted HR, 1.13 [95% CI, 1.09-1.18]), higher all-cause readmission (40.8% vs 38.4%; adjusted HR, 1.08 [95% CI, 1.05-1.12]), and higher all-cause mortality or readmission (56.0% vs 52.1%; adjusted HR, 1.09 [95% CI, 1.06-1.12]). The 34 367 patients (55.9%) who were treated with tPA and had door-to-needle times of longer than 60 minutes, compared with those treated within 60 minutes, had significantly higher all-cause mortality (35.8% vs 32.1%, respectively; adjusted hazard ratio [HR], 1.11 [95% CI, 1.07-1.14]), higher all-cause readmission (41.3% vs 39.1%; adjusted HR, 1.07 [95% CI, 1.04-1.10]), and higher all-cause mortality or readmission (56.8% vs 53.1%; adjusted HR, 1.08 [95% CI, 1.05-1.10]). Every 15-minute increase in door-to-needle times was significantly associated with higher all-cause mortality (adjusted HR, 1.04 [95% CI, 1.02-1.05]) within 90 minutes after hospital arrival, but not after 90 minutes (adjusted HR, 1.01 [95% CI, 0.99-1.03]), higher all-cause readmission (adjusted HR, 1.02; 95% CI, 1.01-1.03), and higher all-cause mortality or readmission (adjusted HR, 1.02 [95% CI, 1.01-1.03]). Conclusions and Relevance: Among patients aged 65 years or older with acute ischemic stroke who were treated with tissue plasminogen activator, shorter door-to-needle times were associated with lower all-cause mortality and lower all-cause readmission at 1 year. These findings support efforts to shorten time to thrombolytic therapy.


Assuntos
Fibrinolíticos/administração & dosagem , Readmissão do Paciente/estatística & dados numéricos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Tempo para o Tratamento , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Causas de Morte , Feminino , Seguimentos , Humanos , Incidência , Infusões Intravenosas , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Terapia Trombolítica
11.
Arch Biochem Biophys ; 689: 108411, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32450066

RESUMO

The process of ischemia/reperfusion (IR) in ischemic stroke often leads to significant cell death and permanent neuronal damage. Safe and effective treatments are urgently needed to mitigate the damage caused by IR injury. The naturally occurring pleiotropic peptide phoenixin 14 (PNX-14) has recently come to light as a potential treatment for IR injury. In the present study, we examined the effects of PNX-14 on several key processes involved in ischemic injury, such as pro-inflammatory cytokine expression, oxidative stress, and the related cascade mediated through the toll-like receptor 4 (TLR4) pathway, using BV2 microglia exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). Our results demonstrate an acute ability of PNX-14 to regulate the expression levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). PNX-14 also prevented oxidative stress by reducing the generation of reactive oxygen species (ROS) and increasing the level of the antioxidant glutathione (GSH). Importantly, PNX-14 inhibited high-mobility group box 1 (HMGB1)/TLR4/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway, by inhibiting the activation of TLR4 and preventing the nuclear translocation of p65 protein. We further confirmed the cerebroprotective effects of PNX-14 in an MCAO rat model, which resulted in reduced infarct volume and decreased microglia activation. Together, the results of this study implicate a possible protective role of PNX-14 against various aspects of IR injury in vitro.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Hormônios Hipotalâmicos/uso terapêutico , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Hormônios Peptídicos/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Isquemia Encefálica/patologia , Linhagem Celular , Masculino , Microglia/patologia , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia
12.
Medicine (Baltimore) ; 99(20): e20307, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443379

RESUMO

INTRODUCTION: Uncertainty remains regarding the impact of enteric-coated (EC) aspirin as it relates to the reduction of cardiovascular risk. We hypothesize that EC formulation based on a previous report may blunt aspirin response as evidenced by reduced Thromboxane A2 (TXA 2) levels in diabetic patients. Thus, it was imperative to ascertain and validate the effect of the EC formulation of Aspirin on the Thromboxane B2 (TXB2) level. METHODS/DESIGN: An open-label consecutive randomized interventional controlled trial. Patients with newly diagnosed ischemic stroke who are just about to start Aspirin were assessed for eligibility and inclusion in our trial. Consecutive patients (admitted to the stroke unit of Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar) will be randomized to receive either EC aspirin or plain Aspirin. They will be required to continue taking them throughout the study (3 days). Demographics and laboratory records of the study participants will be abstracted from online records. Further study variables will be obtained manually in designated case record forms (CRF). The primary outcomes are the incidence of aspirin non-responders (level of residual serum TXB2 associated with elevated thrombotic risk (<99.0% inhibition or TXB2 >3.1 ng/mL) within 72 h after three daily aspirin doses). Whereas secondary outcomes are the incidence of GIT bleeding of various preparations of Aspirin. The study was approved by MRC and IRB of Hamad Medical Corporation (MRC number: 01-18-156). DISCUSSION: This trial will determine potential differences in the efficacy of EC Aspirin and plain Aspirin on the Thromboxane B2 level. Additionally, it will ascertain the tolerability and safety of both formulations of Aspirin in patients with newly diagnosed ischemic stroke. These results will either support the current notion of no difference between the two formulations. However, if a difference is found, this will invite for future trials exploring clinical outcomes occurrence between various formulations. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT04330872 registered on April 2, 2020.


Assuntos
Aspirina/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Adolescente , Adulto , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Plaquetas/efeitos dos fármacos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Método Simples-Cego , Fatores Socioeconômicos , Comprimidos com Revestimento Entérico , Tromboxano B2/sangue , Adulto Jovem
14.
Mol Immunol ; 123: 74-87, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32438202

RESUMO

BACKGROUND: Idebenone is a well-appreciated mitochondrial protectant while the mechanisms underlying the neuroprotection in cerebral ischemia and reperfusion (I/R) remain elusive. It has been manifested NLRP3 inflammasom activation contributed to I/R induced damage. It raises questions how exactly NLRP3 inflammasom was activated in microglia and neuron and whether idebenone reverses the process in I/R. METHODS: I/R rat model was utilized and BV2, primary microglia and PC12 cells were subjected to oxygen-glucose deprivation (OGD). Then, western-blotting, q-PCR, immunofluorescence staining, ELISA, flow cytometry and immunoprecipitation analysis were performed. RESULTS: We found ROS-NLRP3 singaling was activated in BV2 cells at OGD/R 24 h. Importantly, microglial NLRP3 activation was essential for NLRP3 activation in PC12 cells under microglial-neuronal co-culture circumstance, which has been confirmed to induced neuronal apoptosis. Further, we found mitochondrial dysfunction in OGD/R led to mt-DNA translocation as well as generation of mt-ROS, resulting cytosolic accumulation of oxidized mt-DNA. Ultimately, oxidized mt-DNA binding to NLRP3 contributed to further activation of NLRP3 and dramatically augmented inflammation in BV2 and PC12 cells. Furthermore, idebenone treatment inhibited the process, thus suppressing the NLRP3-mediated inflammatory injury after OGD/R. In vivo, NLRP3 was activated in microglia of I/R rats and inhibition of NLRP3 was observed in idebenone treatment group, which had less neurological deficit and less infarct volume. INTERPRETATION: Our data revealed the anti-inflammatory effects of idebenone via suppressing activation of NLRP3 and ameliorating NLRP3-mediating damage in I/R, which may provide new insight in therapeutic strategy for ischemic stroke.


Assuntos
Isquemia Encefálica , Encefalite/prevenção & controle , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuroproteção/efeitos dos fármacos , Traumatismo por Reperfusão , Ubiquinona/análogos & derivados , Animais , Animais Recém-Nascidos , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/imunologia , Isquemia Encefálica/metabolismo , Células Cultivadas , Encefalite/etiologia , Inflamassomos/metabolismo , Inflamassomos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células PC12 , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico
16.
Womens Health (Lond) ; 16: 1745506520922760, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32459136

RESUMO

BACKGROUND: Clinical factors associated with exclusion from recombinant tissue plasminogen activator in both men and women are not completely understood. The aim of this study is to determine whether there is a gender difference in clinical risk factors that excluded ischemic stroke patients with a history of smoking from recombinant tissue plasminogen activator. METHODS: Retrospective data from a stroke registry were analyzed, and multivariable linear regression models were used to determine gender differences. Logistic regression models determined exclusion clinical risk factors for thrombolysis in male and female acute ischemic stroke patients with a history of smoking, while sequentially adjusting for sociodemographic, clinical, and stroke-related variables. The Kaplan-Meier survival analysis was used to determine the exclusion probabilities of men and women with a history of smoking within the stroke population. RESULTS: Of the 1,446 acute ischemic stroke patients eligible for recombinant tissue plasminogen activator, 379 patients with a history of smoking were examined, of which 181 received recombinant tissue plasminogen activator while 198 were excluded from receiving recombinant tissue plasminogen activator. Of the 198 patients, 75 females and 123 males were excluded from receiving recombinant tissue plasminogen activator. After multivariable adjustment for age, National Institutes of Health scores, and stroke-related factors, females who present with weakness/paresis on initial examination (OR = 0.117, 95% CI, 0.025-0.548) and men who present with a history of previous transient ischemic attack (OR = 0.169, 95% CI, 0.044-0.655), antiplatelet medication use (OR = 0.456, 95% CI, 0.230-0.906), and weakness/paresis on initial examination (OR = 0.171, 95% CI, 0.056-0.521) were less likely to be excluded from recombinant tissue plasminogen activator (thrombolysis therapy). CONCLUSIONS: In an ischemic stroke population with a history of smoking, female smokers are more likely to be excluded from thrombolysis therapy in comparison to men, even after adjustment for confounding variables.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fumar/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Terapia Trombolítica , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico
17.
BMC Neurol ; 20(1): 197, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32429850

RESUMO

BACKGROUND: Acute ischemic stroke attack with and without a recent TIA may differ in clinical risk factors, and this may affect treatment outcomes following thrombolytic therapy. We examined whether the odds of exclusion or inclusion for thrombolytic therapy are greater in ischemic stroke with TIA less than 24 h preceding ischemic stroke (recent-TIA) as compared to those without recent TIA or non-TIA > 24 h and less than 1 month (past-TIA). METHODS: A retrospective hospital-based analysis was conducted on 6315 ischemic stroke patients, of whom 846 had proven brain diffusion-weighted magnetic resonance imaging (DW-MRI) of an antecedent TIA within 24 h prior to ischemic stroke. The logistic regression model was developed to generate odds ratios (OR) to determine clinical factors that may increase the likelihood of exclusion or inclusion for thrombolytic therapy. The validity of the model was tested using a Hosmer-Lemeshow test, while the Receiver Operating Curve (ROC) was used to test the sensitivity of our model. RESULTS: In the recent-TIA ischemic stroke population, patients with a history of alcohol abuse (OR = 5.525, 95% CI, 1.003-30.434, p = 0.05), migraine (OR = 4.277, 95% CI, 1.095-16.703, p = 0.037), and increasing NIHSS score (OR = 1.156, 95% CI, 1.058-1.263, p = 0.001) were associated with the increasing odds of receiving rtPA, while older patients (OR = 0.965, 95% CI, 0.934-0.997, P = 0.033) were associated with the increasing odds of not receiving rtPA. CONCLUSION: In recent-TIA ischemic stroke patients, older patients with higher INR values are associated with increasing odds of exclusion from thrombolytic therapy. Our findings demonstrate clinical risks factors that can be targeted to improve the use and eligibility for rtPA in in recent-TIA ischemic stroke patients.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Ataque Isquêmico Transitório/epidemiologia , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Terapia Trombolítica/métodos , Resultado do Tratamento
18.
Stroke ; 51(6): 1805-1812, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32389068

RESUMO

Background and Purpose- The mobile stroke unit (MSU) brings imaging and thrombolysis to patients in the field. The MSU has the potential to decrease time from onset to thrombolysis; however, this depends on the location of the patient, the MSU, and the hospital. The MSU will only be able to treat a small subset of patients it is dispatched to. Using conditional probability modeling, we evaluate in which scenarios the MSU exhibits clear benefit over the direct-to-mothership method. Methods- Previously published conditional probability models for drip-and-ship versus mothership transport were modified to reflect MSU workflow. It was assumed that the MSU was dispatched from the endovascular therapy center. Eight scenarios were generated, varying treatment efficiency on the MSU and at the endovascular therapy center and the threshold for dispatching the MSU (low threshold: low treatment rate but few missed patients; high threshold: higher treatment rate, potential for missed treatment opportunities). Results- The relative difference in outcomes between the MSU and mothership was small. Geographic areas where the MSU is superior to mothership increase in size as treatment time on the MSU decreases. When a high-threshold dispatch system is used, the area where the MSU is superior decreases, but the relative difference in predicted outcomes between the MSU and mothership increases. The largest relative difference favoring the MSU was found in areas where the patient would forgo access to alteplase, based upon a 4.5-hour treatment threshold, using mothership transport. Conclusions- There are few scenarios where MSU transport predicts substantially superior outcomes to the mothership method when the MSU is dispatched from the endovascular therapy center. Outcomes using the MSU are maximized when dispatch criteria that maximize patients eligible for thrombolysis treatment are used and treatment times on the MSU are short relative to those of the endovascular therapy center.


Assuntos
Isquemia Encefálica , Unidades Móveis de Saúde , Modelos Teóricos , Acidente Vascular Cerebral , Terapia Trombolítica , Tempo para o Tratamento , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia
20.
Biomed Khim ; 66(2): 145-150, 2020 Feb.
Artigo em Russo | MEDLINE | ID: mdl-32420895

RESUMO

Ischemic stroke is one of the most socially important diseases characterized by impaired cerebral circulation with focal damage of the brain tissue and decreased functionality. Despite the successes of modern pharmacology, possibilities of pharmacotherapy for stroke remain limited, and the research for new drugs with neuroprotective effects that can prevent brain cell death is still relevant. In this study we have investigated the neuroprotective activity of ubiquinol as a part of an innovative form on a rat model of irreversible 24 h-cerebral ischemia with evaluation of the mechanisms of its neuroprotective effect. Ubiquinol (30 mg/kg), administered intravenously in the acute period of irreversible 24 h focal cerebral ischemia, had a direct neuroprotective effect, characterized by a decrease in the volume of brain tissue necrosis. The protective effect of ubiquinol is due to its ability to inhibit the development of oxidative stress by the direct anti-radical action, preventing the increase in the lipid hydroperoxide content in the brain tissue adjacent to the focus of necrosis, lowering the lipid oxidation rate in plasma against under conditions of increased total antioxidant activity in the brain and blood of experimental animals. In vitro experiments have shown the ability of ubiquinol to prevent cell death in primary culture of cerebral neurons of rat brain under 4 h oxygen/glucose deprivation followed by 20 h reoxygenation.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Ubiquinona/análogos & derivados , Animais , Antioxidantes/análise , Neurônios/citologia , Neurônios/efeitos dos fármacos , Estresse Oxidativo , Cultura Primária de Células , Ratos , Ubiquinona/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA