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1.
BMC Neurol ; 21(1): 18, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435910

RESUMO

BACKGROUND: Dorsolateral medullary infarction is a typical cerebral infarction which is characterized by Wallenberg's syndrome. Neurotrophic keratopathy is an uncommon consequence of dorsolateral medullary infarction. At present, the protocol is aimed to study the dynamic changes in corneal innervation and the ocular surface environment after dorsolateral medullary infarction. METHODS: This study will involve consecutive data from all medical records of patients within 7 days of acute dorsolateral medullary infarction onset at the Departments of Neurology from 10 collaborating stroke centers. Eligible patients will mainly be characterized based on detailed physical examinations, multimodal imaging, and corneal related examinations and patients will be followed-up for 2 years. Neurotrophic keratopathy after dorsolateral medullary infarction is the primary endpoint. The dynamic histological corneal innervation and ocular surface environment after dorsolateral medullary infarction will be observed during the follow-up period. DISCUSSION: This multicentric, prospective registry is the first to identify and characterize the dynamic changes of corneal innervation and the ocular surface environment after acute dorsolateral medullary infarction. The significance of the study is to emphasize that the curative effect is based on the doctors' identification of the disease in the earliest stage before irreversible damage occurs to the cornea. TRIAL REGISTRATION: The registry was registered ( ChiCTR-OPC-17,011,625 ) on June 11, 2017.


Assuntos
Infarto Cerebral/complicações , Infarto Cerebral/patologia , Doenças da Córnea/etiologia , Sistema de Registros , Adulto , Feminino , Humanos , Masculino , Bulbo/patologia , Pessoa de Meia-Idade
2.
Medicine (Baltimore) ; 99(50): e23577, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327318

RESUMO

OBJECTIVE: Atorvastatin and aspirin have been used in treating different forms of epilepsy. However, their effect on post-stroke epilepsy (PSE) still needs to be validated by large-scale clinical studies. In addition, their impact on the use of the antiepileptic drug levetiracetam for post-stroke epilepsy remains to be explored. Thus, the aim of this study was to further evaluate the effect of atorvastatin and aspirin on PSE and their effect on the usage of the antiepileptic drug levetiracetam in PSE patients. METHODS: Patients, aged 65 to 85 years, with newly diagnosed post-ischemic stroke epilepsy from August 30, 2014 to August 30, 2018 were included in the study, with the exclusion of those with coexisting conditions. RESULTS: Initially, 1321 patients were included, and 780 remained in the study at the 1-year follow-up. During the study, atorvastatin treatment with or without aspirin reduced the number of clinical epileptic episodes in PSE patients. It also reduced the dosage of levetiracetam and achieved better control of epilepsy compared to levetiracetam mono-treatment. Aspirin co-treatment with levetiracetam did not result in a significant improvement. However, the combination of aspirin with atorvastatin significantly reduced the number of seizures compared to atorvastatin treatment alone. CONCLUSION: Atorvastatin and aspirin co-treatment with levetiracetam can reduce epilepsy in PSE patients and reduce the dosage of levetiracetam required for effective control of PSE.


Assuntos
Anticonvulsivantes/uso terapêutico , Aspirina/uso terapêutico , Atorvastatina/uso terapêutico , Epilepsia/tratamento farmacológico , Levetiracetam/uso terapêutico , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Aspirina/administração & dosagem , Atorvastatina/administração & dosagem , Infarto Cerebral/complicações , Infarto Cerebral/patologia , Quimioterapia Combinada , Epilepsia/etiologia , Feminino , Humanos , Levetiracetam/administração & dosagem , Masculino , Índice de Gravidade de Doença , Acidente Vascular Cerebral/patologia
3.
J Rehabil Med ; 52(10): jrm00116, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33043382

RESUMO

OBJECTIVE: A better understanding of factors influencing breathing weakness in stroke survivors would help in planning rehabilitation therapies. The main objective of this study was to determine whether the location of cerebral infarct is associated with breathing weakness in patients with subacute stroke. DESIGN: Cross-sectional analysis of a prospective cohort. PATIENTS: Consecutive patients admitted to a neurology rehabilitation unit with first-time ischaemic stroke (n?=?170). METHODS: Breathing weakness was defined as >?70% reduction in maximal inspiratory and expiratory pressures (PImax and PEmax, respectively) compared with reference values. Computed tomography and magnetic resonance imaging were used to locate stroke lesions, which were classified as cortical, subcortical, cortico-subcortical, brainstem, or cerebellum. The affected cerebrovascular territory was identified to classify stroke subtype. The association between maximal respiratory pressure and affected brain area was studied using median regression analysis. RESULTS: Breathing weakness was detected in 151 (88.8%) patients. Those with cortical and cortico-subcortical stroke location had the lowest PImax and PEmax values (median 33 cmH2O). This value differed significantly from maximal respiratory pressures of patients with strokes located in the brainstem and the cerebellum, with PImax median differences (?) of 16 cmH2O (95% confidence interval (95% CI) 4.127.9) and 27 cmH2O (95% CI 7.846.2), respectively, and PEmax median differences of 27 cmH2O (95% CI 11.442.7) and 49 cmH2O (95% CI 23.774.3), respectively, both of which remained significant after adjustments. CONCLUSION: The prevalence of breathing weakness was very high in stroke patients admitted to a neurorehabilitation ward, being more severe in cortical or cortico-subcortical stroke.


Assuntos
Encéfalo/patologia , Infarto Cerebral/patologia , Dispneia/patologia , Respiração , Acidente Vascular Cerebral/patologia , Idoso , Encéfalo/diagnóstico por imagem , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico por imagem , Estudos de Coortes , Estudos Transversais , Dispneia/diagnóstico por imagem , Dispneia/epidemiologia , Feminino , Humanos , Masculino , Pressões Respiratórias Máximas , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Análise de Regressão , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Reabilitação do Acidente Vascular Cerebral/estatística & dados numéricos
4.
Inflamm Res ; 69(12): 1201-1213, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32944799

RESUMO

OBJECTIVE AND DESIGN: Microglia stimulated by oxygen glucose deprivation (OGD) were treated with quercetin to investigate the effect on oxidative stress and the inflammatory response and to explore whether toll-like receptor 4 (TLR4) signaling was involved. In addition, the effect of quercetin on the neurological functions of neonatal mice with hypoxic-ischemic brain injury (HIBI) was examined. MATERIALS AND SUBJECTS: Mouse BV2 microglial cells and postnatal day 7 neonatal mice were used. TREATMENT: A predetermined concentration of quercetin was used in cell experiments. Quercetin was injected i.p. (50 mg/kg) at three time points after HI insult: 0, 24, and 48 h. METHODS: Cell viability assay, Western blotting, qRT-RCR, ELISA, HIBI model construction and behavioral tests. RESULTS: This study first showed that quercetin protected BV2 cells from OGD-induced damage and reversed the changes in microglial oxidative stress-related molecules. Second, quercetin inhibited OGD-induced expression of inflammatory factors in BV2 cells and suppressed TLR4/MyD88/NF-κB signaling. Finally, quercetin was disclosed to be effective in mitigating cerebral infarct volume and cognitive and motor function deficits in HIBI mice. CONCLUSION: These results suggest that the neuroprotective effect of quercetin in HIBI mice is partially due to the inhibition of oxidative stress and TLR4-mediated inflammatory responses in activated microglia.


Assuntos
Antioxidantes/uso terapêutico , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Microglia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quercetina/uso terapêutico , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Linhagem Celular , Infarto Cerebral/patologia , Hipóxia-Isquemia Encefálica/psicologia , Camundongos , Fator 88 de Diferenciação Mieloide/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
5.
Stroke ; 51(9): e193-e202, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32781941

RESUMO

BACKGROUND AND PURPOSE: We aim to examine effects of collateral status and post-thrombectomy reperfusion on final infarct distribution and early functional outcome in patients with anterior circulation large vessel occlusion ischemic stroke. METHODS: Patients with large vessel occlusion who underwent endovascular intervention were included in this study. All patients had baseline computed tomography angiography and follow-up magnetic resonance imaging. Collateral status was graded according to the criteria proposed by Miteff et al and reperfusion was assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) system. We applied a multivariate voxel-wise general linear model to correlate the distribution of final infarction with collateral status and degree of reperfusion. Early favorable outcome was defined as a discharge modified Rankin Scale score ≤2. RESULTS: Of the 283 patients included, 129 (46%) had good, 97 (34%) had moderate, and 57 (20%) had poor collateral status. Successful reperfusion (mTICI 2b/3) was achieved in 206 (73%) patients. Poor collateral status was associated with infarction of middle cerebral artery border zones, whereas worse reperfusion (mTICI scores 0-2a) was associated with infarction of middle cerebral artery territory deep white matter tracts and the posterior limb of the internal capsule. In multivariate regression models, both mTICI (P<0.001) and collateral status (P<0.001) were among independent predictors of final infarct volumes. However, mTICI (P<0.001), but not collateral status (P=0.058), predicted favorable outcome at discharge. CONCLUSIONS: In this cohort of patients with large vessel occlusion stroke, both the collateral status and endovascular reperfusion were strongly associated with middle cerebral artery territory final infarct volumes. Our findings suggesting that baseline collateral status predominantly affected middle cerebral artery border zones infarction, whereas higher mTICI preserved deep white matter and internal capsule from infarction; may explain why reperfusion success-but not collateral status-was among the independent predictors of favorable outcome at discharge. Infarction of the lentiform nuclei was observed regardless of collateral status or reperfusion success.


Assuntos
Arteriopatias Oclusivas/patologia , Arteriopatias Oclusivas/terapia , Infarto Cerebral/patologia , Infarto Cerebral/terapia , Circulação Colateral , Procedimentos Endovasculares/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/terapia , Modelos Lineares , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reperfusão , Estudos Retrospectivos , Acidente Vascular Cerebral/terapia , Trombectomia , Resultado do Tratamento , Substância Branca/patologia
6.
Stroke ; 51(9): e223-e226, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32684144

RESUMO

BACKGROUND AND PURPOSE: Ischemic infarction of the corpus callosum is rare and infarction isolated to the corpus callosum alone rarer still, accounting for much <1% of ischemic stroke in most stroke registries. About half of callosal infarctions affect the splenium. METHODS: During a 2-week period, at the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City, 4 patients at Montefiore Medical Center in the Bronx were found to have ischemic lesions of the splenium of the corpus callosum, 2 with infarction isolated to the corpus callosum. RESULTS: All patients tested positive for COVID-19 and 3 had prolonged periods of intubation. All had cardiovascular risk factors. Clinically, all presented with encephalopathy and had evidence of coagulopathy and raised inflammatory markers. CONCLUSIONS: Infarction of the splenium of the corpus callosum is exceedingly rare and a cluster of such cases suggests COVID-19 as an inciting agent, with the mechanisms to be elucidated.


Assuntos
Infarto Cerebral/complicações , Infarto Cerebral/patologia , Infecções por Coronavirus/complicações , Corpo Caloso/patologia , Pneumonia Viral/complicações , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Complicações do Diabetes/complicações , Evolução Fatal , Feminino , Humanos , Hipertensão/complicações , Hipotireoidismo/complicações , Inflamação/sangue , Intubação Intratraqueal , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Reabilitação do Acidente Vascular Cerebral
7.
PLoS One ; 15(7): e0235765, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32667947

RESUMO

Automatic evaluation of 3D volumes is a topic of importance in order to speed up clinical decision making. We describe a method to classify computed tomography scans on volume level for the presence of non-acute cerebral infarction. This is not a trivial task, as the lesions are often similar to other areas in the brain regarding shape and intensity. A three stage architecture is used for classification: 1) A cranial cavity segmentation network is developed, trained and applied. 2) Region proposals are generated 3) Connected regions are classified using a multi-resolution, densely connected 3D convolutional network. Mean area under curve values for subject level classification are 0.95 for the unstratified test set, 0.88 for stratification by patient age and 0.93 for stratification by CT scanner model. We use a partly segmented dataset of 555 scans of which 186 scans are used in the unstratified test set. Furthermore we examine possible dataset bias for scanner model and patient age parameters. We show a successful application of the proposed three-stage model for full volume classification. In contrast to black-box approaches, the convolutional network's decision can be further assessed by examination of intermediate segmentation results.


Assuntos
Algoritmos , Infarto Cerebral/classificação , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Redes Neurais de Computação , Tomografia Computadorizada por Raios X/métodos , Idoso , Automação , Estudos de Casos e Controles , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Feminino , Humanos , Masculino , Estudos Retrospectivos
8.
BMC Neurol ; 20(1): 249, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32560642

RESUMO

BACKGROUND: Cerebral venous sinus thrombosis (CVST), a rare cause of cerebral infarction, is often unrecognized at initial presentation. We report the case of a patient with bilateral corpus callosum and corona radiata infarction due to cerebral venous sinus thrombosis presenting as headache and acute reversible aphasia. CASE PRESENTATION: A 30-year-old female patient presented with headache, vomiting, and motor aphasia. She was 20 days post-partum and had a lower than normal food intake following a normal vaginal delivery. Brain magnetic resonance images revealed a bilateral corpus callosum and corona radiata infarction. MR venography (MRV) and digital subtraction angiography (DSA) images showed a signal void in the anterior aspect of the superior sagittal sinus and inferior sagittal sinus, ophthalmic vein expansion, and the reversed direction of venous flow. In addition, images showed non-visualization of the left transverse sinus. The left slender sigmoid sinus and small internal jugular vein were also noted. The diagnosis of cerebral venous thrombosis was considered based on the above findings. The patient was managed with anticoagulation therapy, and recovered substantially after treatment. CONCLUSIONS: Bilateral corpus callosum and corona radiata infarction is very rare. However, for patients who clinically show cranial hypertension and neurological deficits during the puerperium period, the possibility of CVST should be considered. Furthermore, DSA plays an important role in the diagnosis of CVST, and should be routinely checked. Early diagnosis is crucial for the patient suffering from CVST.


Assuntos
Infarto Cerebral/etiologia , Trombose dos Seios Intracranianos/complicações , Adulto , Afasia/etiologia , Encéfalo/patologia , Infarto Cerebral/patologia , Corpo Caloso/patologia , Feminino , Cefaleia/etiologia , Humanos , Período Pós-Parto
9.
World Neurosurg ; 139: e748-e753, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32353539

RESUMO

BACKGROUND: Despite increasing interest in endovascular therapy (EVT) for large-core strokes, little is known about the predictors of good outcome in these patients. The aim of this study was to analyze patients with large-core strokes post-EVT and to define the predictors of favorable outcome in this population. METHODS: A retrospective analysis of prospectively collected data on anterior circulation strokes undergoing EVT between January 2015 and February 2018 was performed. Patients with good baseline functional status who underwent EVT for occlusion of an anterior circulation artery and achieved successful recanalization (modified Treatment in Cerebral Ischemia score ≥2b) but had large follow-up infarct volume (FIV ≥70 cm3) were included in the study. Demographic characteristics, clinical and radiologic data, treatment and postprocedural outcomes were extracted and analyzed. The primary outcome was 90-day modified Rankin Scale (mRS) score, stratified by favorable (mRS 0-3) versus unfavorable (mRS 4-6). RESULTS: Of 355 patients meeting inclusion criteria, 85 (24%) had large FIV on follow-up imaging after EVT and constituted the study cohort. No patients achieved mRS score 0-2 at hospital discharge; 32% had 90-day mRS score 0-3. On multivariate logistic regression analysis, lower FIV (OR, -0.96 [0.95-0.99]; P = 0.007), male sex (OR, -1.29 [1.07-12.3]; P = 0.026), and intravenous tissue plasminogen activator use (OR, 3.6 [2.01-8.9]; P = 0.003) were independent predictors of favorable outcome. Independent predictors of mortality on multivariate analysis were higher FIV (OR, -1.01 [1.007-1.02]; P = 0.001) and female sex (OR, 4.08 [1.25-13.3]; P = 0.02). CONCLUSIONS: For patients with large-core strokes (≥70 cm3) after EVT, approximately one third have favorable outcome at 90 days. Independent predictors of favorable 90-day outcomes include male sex, intravenous tissue plasminogen activator use, and lower FIV.


Assuntos
Recuperação de Função Fisiológica , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Idoso , Infarto Cerebral/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Rinsho Shinkeigaku ; 60(6): 397-406, 2020 Jun 06.
Artigo em Japonês | MEDLINE | ID: mdl-32435049

RESUMO

The lenticulostriate arteries (LSA) supply the lateral half of the head of the caudate nucleus, entire putamen, anterior limb, genu and the superior part of the internal capsule (IC) and a part of the corona radiata. The LSA consists with medial, intermediate and lateral branches. The medial branches perfuse the lateral segment of the globus pallidus, the head of the caudate nucleus and the anterior limb of the IC. The intermediate branches supply the anterior half of the LSA territory, while the lateral branches supply the posterior half. The anterior cerebral artery (ACA) perforators, predominantly Heubner's artery, perfuse the inferomedial part of the caudate head, the anteromedial part of putamen, the anterior part of the lateral segment of the globus pallidus and anterior limb of the internal capsule. Such territories can be represented by the anterior and ventral basal ganglions. The anterior choroidal artery (AChA) gives off three main groups of branches including the lateral branches that supply the medial temporal lobe, the medial branches that supply the cerebral peduncle and the superior branches that supply the internal capsule and the basal ganglia. The superior branches are further discriminated into proximal branches that supply the anterior one third of the posterior limb of internal capsule (PLIC) and the medial segment of the globus pallidus and distal branches that supply the posterior two-third of PLIC, retro-lenticular part of the internal capsule and the lateral thalamic nuclei. The superficial penetrating arteries, i.e. medullary arteries, arise from the cortical branches of the middle cerebral artery (MCA) and supply the deep white matter. Infarcts caused by the medullary artery occlusion are located in the centrum-semiovale and half of them were caused by embolic mechanism. The centrum-semiovale corresponds to cortical border-zone (BZ) while the corona radiate corresponds to internal BZ.


Assuntos
Encéfalo/irrigação sanguínea , Artérias Cerebrais/anatomia & histologia , Infarto Cerebral/patologia , Infarto Cerebral/etiologia , Humanos
11.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(3. Vyp. 2): 29-32, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32307427

RESUMO

INTRODUCTION: Ischemic stroke is one of the most severe neurological pathologies with high mortality and disability. In this connection, the development and study of new drugs for the prevention and treatment of stroke is an extremely important task. A new approach to neuroprotection is the use of lithium salts with antioxidant activity. AIM: To study the cerebroprotective effect of lithium ascorbate on a rat model of ischemic stroke. MATERIAL AND METHODS: Test samples of lithium ascorbate were synthesized ex tempore for an experiment using reagents of ACS qualification (Sigma-Aldrich). The ischemic stroke model was realized using the filament occlusion of the middle cerebral artery in rats of the Sprague Dawley line according to standardized procedure. Neurological examination of the animals, histological study of brain tissue with staining of brain sections, and calculating the volume of cerebral infarction were performed. RESULTS AND CONCLUSION: There is a significant cerebroprotective effect of lithium ascorbate expressed in a multiple decrease in the volume of the zone of cerebral infarction (by 75% of the control group indicator) and the absence of mortality in the experimental group of animals. Newly discovered distinct anti-stroke effect of lithium ascorbate in combination with low toxicity could be considered promising for further clinical studies and practical application in neurology.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/prevenção & controle , Modelos Animais de Doenças , Compostos de Lítio/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Animais , Isquemia Encefálica/patologia , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/patologia , Compostos de Lítio/farmacologia , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/patologia
12.
J Integr Neurosci ; 19(1): 119-123, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32259892

RESUMO

The effectiveness of repetitive transcranial magnetic stimulation on the post-stroke motor recovery is not apparent. To perform an accurate evaluation, we adjusted for critical factors that determine motor outcomes, including lesion location and the state of the corticospinal tract. We only included patients with cerebral infarct in the corona radiata and with corticospinal tract interruption, apparent on diffusion tensor tractography. We retrospectively enrolled 34 patients whose diffusion tensor tractography corticospinal tract was interrupted by a cerebral infarct. The corticospinal tract state of each patient was evaluated using diffusion tensor tractography. Of the 34 patients whose corticospinal tract was interrupted on diffusion tensor tractography, 12 patients underwent repetitive transcranial magnetic stimulation treatment at the early stage after cerebral infarct (repetitive transcranial magnetic stimulation group). In comparison, 22 patients did not receive repetitive transcranial magnetic stimulation treatment (non-repetitive transcranial magnetic stimulation group). High-frequency repetitive transcranial magnetic stimulation (10 Hz) was performed on the primary motor cortex of the affected hemisphere. At the six month evaluation after the onset of the infarct, motor function was measured in each patient. In both groups, compared to their states during the initial evaluation, significant improvement was found in all measurements of motor function. However, six months after onset, no significant differences between the two groups were found in these measurement scores. When a patient's CST is interrupted, high-frequency repetitive transcranial magnetic stimulation treatment at the early stage after cerebral infarct might have no additional therapeutic effect on motor outcome. Qualified randomized controlled trials are needed to support our findings further.


Assuntos
Encéfalo/patologia , Infarto Cerebral/patologia , Reabilitação do Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Idoso , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Substância Branca/patologia
13.
J Stroke Cerebrovasc Dis ; 29(5): 104668, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32184024

RESUMO

BACKGROUND: The purpose of this study was to evaluate the natural recovery process and tissue injury associated with cerebral hemorrhage and cerebral infarction, which were induced to the same degree, in the striatum of rats. METHODS: Male Wistar rats were divided into intracerebral hemorrhagic (ICH) and ischemia (ISC) groups, with the ICH group injected with a collagenase solution and the ISC group injected with an endothelin-1 solution. In the SHAM group, physiological saline was injected. Motor function was evaluated by the ladder and forelimb placing tests on the first day before surgery and the first, seventh, and 14th day after surgery. On day 15 after surgery, brain tissue was harvested and frozen sections were prepared. Nissl staining was performed, and the tissue loss, ventricular, and hemispheric volumes were analyzed. RESULTS: On the first day of surgery, the ICH group had significantly decreased motor function compared with the ISC group. However, subsequent recovery of motor function was faster in the ICH group than that in the ISC group. In addition, tissue loss and hemispheric volumes were significantly higher in the ISC group than those in the ICH group, whereas the ventricular volume was significantly higher in the ICH group than that in the ISC group. CONCLUSIONS: Collectively, our findings indicate that, in ICH and ISC where the brain damage involves the same site and is approximately the same size, motor function is recovered faster in ICH than that in ISC. As such, differences in secondary degeneration are likely affected.


Assuntos
Hemorragia dos Gânglios da Base/fisiopatologia , Infarto Cerebral/fisiopatologia , Corpo Estriado/irrigação sanguínea , Corpo Estriado/fisiopatologia , Membro Anterior/inervação , Atividade Motora , Animais , Hemorragia dos Gânglios da Base/patologia , Infarto Cerebral/patologia , Corpo Estriado/patologia , Modelos Animais de Doenças , Masculino , Ratos Wistar , Recuperação de Função Fisiológica , Fatores de Tempo
14.
Curr Pharm Biotechnol ; 21(10): 955-963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32039676

RESUMO

BACKGROUND: Glial Maturation Factor Beta (GMFB) is a highly conserved brain-enriched protein implicated in immunoregulation, neuroplasticity and apoptosis, processes central to neural injury and repair following cerebral ischaemia. Therefore, we examined if changes in neurocellular GMFB expression and release can be used to assess brain injury following ischaemia. METHODS AND RESULTS: Immunofluorescence staining, Western blotting, immunohistochemistry and ELISA were used to measure GMFB in cultured neurons and astrocytes, rat brain tissues and plasma samples from stroke model rats and stroke patients, while cell viability assays, TTC staining and micro- PET were used to assess neural cell death and infarct severity. Immunofluorescence and immunohistochemistry revealed GMFB expression mainly in astrocyte and neuronal nuclei but also in neuronal axons and dendrites. Free GMFB concentration increased progressively in the culture medium during hypoxia-hypoglycaemia treatment. Plasma GMFB concentration increased in rats subjected to middle cerebral artery occlusion (MCAO, a model of stroke-reperfusion) and in stroke patients. Plasma GMFB in MCAO model rats was strongly correlated with infarct size (R2=0.9582). Plasma GMFB concentration was also markedly elevated in stroke patients within 24 h of onset and remained elevated for more than one week. Conversely, plasma GMFB elevations were not significant in myocardial infarct patients and stroke patients without infarction. CONCLUSION: GMFB has the prerequisite stability, expression specificity and response dynamics to serve as a reliable indicator of ischaemic injury in animal models and stroke patients. Plasma GMFB may be a convenient non-invasive adjunct to neuroimaging for stroke diagnosis and prognosis.


Assuntos
Astrócitos/metabolismo , Encéfalo/metabolismo , Infarto Cerebral/sangue , Fator de Maturação da Glia/sangue , Neurônios/metabolismo , Adulto , Animais , Apoptose , Astrócitos/patologia , Encéfalo/patologia , Estudos de Casos e Controles , Morte Celular , Células Cultivadas , Infarto Cerebral/metabolismo , Infarto Cerebral/patologia , Modelos Animais de Doenças , Feminino , Fator de Maturação da Glia/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neurônios/patologia , Valor Preditivo dos Testes , Ratos , Ratos Sprague-Dawley
15.
Nat Neurosci ; 23(3): 351-362, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32042176

RESUMO

Monocyte-derived and tissue-resident macrophages are ontogenetically distinct components of the innate immune system. Assessment of their respective functions in pathology is complicated by changes to the macrophage phenotype during inflammation. Here we find that Cxcr4-CreER enables permanent genetic labeling of hematopoietic stem cells (HSCs) and distinguishes HSC-derived monocytes from microglia and other tissue-resident macrophages. By combining Cxcr4-CreER-mediated lineage tracing with Cxcr4 inhibition or conditional Cxcr4 ablation in photothrombotic stroke, we find that Cxcr4 promotes initial monocyte infiltration and subsequent territorial restriction of monocyte-derived macrophages to infarct tissue. After transient focal ischemia, Cxcr4 deficiency reduces monocyte infiltration and blunts the expression of pattern recognition and defense response genes in monocyte-derived macrophages. This is associated with an altered microglial response and deteriorated outcomes. Thus, Cxcr4 is essential for an innate-immune-system-mediated defense response after cerebral ischemia. We further propose Cxcr4-CreER as a universal tool to study functions of HSC-derived cells.


Assuntos
Isquemia Encefálica/imunologia , Células-Tronco Hematopoéticas/imunologia , Microglia/imunologia , Monócitos/imunologia , Receptores CXCR4/metabolismo , Acidente Vascular Cerebral/imunologia , Animais , Isquemia Encefálica/patologia , Linhagem da Célula , Infarto Cerebral/imunologia , Infarto Cerebral/patologia , Células-Tronco Hematopoéticas/patologia , Imunidade Inata/genética , Ataque Isquêmico Transitório/imunologia , Ataque Isquêmico Transitório/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/patologia , Monócitos/patologia , Receptores CXCR4/genética , Receptores CXCR4/imunologia , Acidente Vascular Cerebral/patologia , Trombose/patologia , Resultado do Tratamento
16.
World Neurosurg ; 138: 608-618, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31953096

RESUMO

This paper used magnetic resonance diffusion kurtosis imaging to observe the acute cerebral infarction model of mice, and studied the imaging changes of ischemic penumbra after perfusion of model for rat middle cerebral artery occlusion experiment, and combined with the physiologic changes of mice. The damage of neurons was evaluated by the evolution of N-methyl-D-aspartate receptors to provide a corresponding imaging basis for the diagnosis and treatment of ischemic penumbra. The research shows that the diffusivity value decreases with time, and the diffusion kurtosis increases with time. The difference in diffusivity between different parts of the same time point and the same part of the same point (except the edge relative to the normal area) is statistically different. Learning significance was set at P < 0.05. The expression of N-methyl-D-aspartate receptor 2A in tissue homogenate increased overall, and expression in synaptic membrane, synaptic membrane, and light membrane decreased. The expression of N-methyl-D-aspartate acid receptor 2B in tissue homogenate, synaptic membrane, and light cell membrane decreased, and it increased first and then decreased in the synaptic membrane. The studies confirmed that magnetic resonance imaging has a certain clinical diagnostic value for the penumbra evolution mechanism and neuronal injury of acute cerebral infarction, which deserves further study.


Assuntos
Infarto Cerebral/terapia , Imagem por Ressonância Magnética/métodos , Técnicas de Sonda Molecular , Células-Tronco Neurais/transplante , Paralisia/terapia , Células-Tronco Pluripotentes/transplante , Animais , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Membro Posterior/diagnóstico por imagem , Membro Posterior/patologia , Sondas Moleculares , Paralisia/diagnóstico por imagem , Ratos
17.
Eur J Pharmacol ; 872: 172944, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31978424

RESUMO

Salvianolate has been widely used for the treatment of cerebrovascular diseases. However, the detailed molecular mechanism of how it alleviates cerebral ischaemia-reperfusion injury is not well understood. In the present study, we investigated the neuroprotective effects of salvianolate in acute cerebral infarction using the PC12 cell oxygen-glucose deprivation (OGD) model in vitro and the rat transient middle cerebral artery occlusion (MCAO) model in vivo. The results showed that the salvianolate significantly reduced the level of reactive oxygen species and inhibited the Caspase-3 signalling pathway in vitro; at the same time, in vivo experiments showed that salvianolate obviously reduced the infarct area (12.9%) and repaired cognitive function compared with the model group (28.28%). In conclusion, our data demonstrated that the salvianolate effectively alleviated cerebral ischaemia-reperfusion injury via suppressing the Caspase-3 signalling pathway.


Assuntos
Caspase 3/metabolismo , Infarto Cerebral/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Técnicas de Observação do Comportamento , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Infarto Cerebral/complicações , Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Modelos Animais de Doenças , Humanos , Masculino , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/uso terapêutico , Ratos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais/efeitos dos fármacos
18.
Gene ; 728: 144285, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31838253

RESUMO

Stroke has serious implications on patients and a huge impact on society. The current treatment regimens with drug for acute cerebral infarction are unsatisfactory. Here, we explore whether the two long non-coding RNA (lncRNA) candidates from preliminary research regulate apoptosis after cerebral infarction, and evaluate the underlying mechanism of action. Bioinformatics analysis of the lncRNA microarray in the preliminary research of our group was performed. Changes in the expression of candidate lncRNAs in SH-SY5Y cells were detected by quantitative polymerase chain reaction (qPCR) after treatment with seven different oxygen and glucose deprivation (OGD) methods. The changes were detected after transfection of cells with six small-interfering RNAs (siRNAs). Cell models were established by OGD after transfection with siRNAs. Cell viability was evaluated with the cell counting kit 8 (CCK8) assay, while TUNEL staining and flow cytometry analysis were performed to determine apoptosis. Changes in the expression and phosphorylation of three proteins were detected by western blotting after the knockdown of NR_120420. Changes in the expression and phosphorylation of P65 protein were detected by western blotting after this cell model was treated with PDTC. Cells were transfected with siNR_120420 and treated with and without PDTC, followed by analysis of cell viability and apoptosis. Bioinformatics analysis revealed that the differentially expressed lncRNAs after acute cerebral infarction were mainly involved in nuclear factor kappa B (NF-κB) and apoptosis. Expression of the two lncRNA candidates in SH-SY5Y cells was the maximum after incubation under the OGD condition for 8 h. The knockdown efficiency was more than 60% for four of the six siRNAs, and knockdown of NR_120420 increased the cell viability and decreased the percentage of TUNEL-positive cells and apoptotic cells. Knockdown of lnc-GCH1-2:3 resulted in none of these effects. Phosphorylation of NF-κB (P65) decreased significantly after the knockdown of NR_120420. Expression and phosphorylation of P65 was significantly reduced after it was treated with PDTC. The inhibitor of NF-κB (PDTC) could abolish the effect of NR_120420 on the regulation of apoptosis in this cell model. Both NR_120420 and lnc-GCH1-2:3 had significant changes in this cell model. Knockdown of NR_120420 inhibited the apoptosis of cells, while NR_120420 knockdown inhibited apoptosis after cerebral infarction by downregulating the phosphorylation of a subunit of NF-κB (P65). This study may provide new idea for improving drug treatment of acute cerebral infarction.


Assuntos
Apoptose , Infarto Cerebral/patologia , Glucose/deficiência , NF-kappa B/metabolismo , Neuroblastoma/patologia , Oxigênio/metabolismo , RNA Longo não Codificante/genética , Doença Aguda , Idoso , Estudos de Casos e Controles , Hipóxia Celular , Proliferação de Células , Infarto Cerebral/genética , Infarto Cerebral/metabolismo , Feminino , Humanos , Masculino , Análise em Microsséries , NF-kappa B/genética , Neuroblastoma/genética , Neuroblastoma/metabolismo , Fosforilação , Transdução de Sinais , Células Tumorais Cultivadas
19.
Curr Pharm Biotechnol ; 21(8): 702-709, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31884927

RESUMO

OBJECTIVE: The purpose of this paper was to study the protective effect of paeoniflorin on acute cerebral ischemia. The animal model of cerebral infarction induced by Middle Cerebral Artery Occlusion (MCAO) was blocked by the suture method. Sixty SD rats were randomly divided into the shame group, MCAO group, paeoniflorin (60, 120, 240 mg/kg, respectively) and Nimodipine (NMDP) group (n = 10 per group). METHODS: The rats were intragastrically administered immediately after the operation. After 7 days of gavage, the brains were decapitated at 24 h. Hematoxylin and Eosin (HE) staining was used to observe the degree of cell damage in the cerebral cortex of rats. Immunohistochemistry was used to detect silver plating and to observe changes in nerve cells. Rats in the model group showed obvious symptoms of neurological deficits, such as the ischemic morphological changed, the Malondialdehyde (MDA), Lactate Dehydrogenase (LD) content and lactate dehydrogenase (LDH) activity were significantly increased in the ischemic brain tissue, while the Superoxide Dismutase (SOD) activity was decreased. RESULTS: The decrease in Na+-K+-ATPase activity was significantly lower than that in the sham group. The neurological symptoms and signs of MCAO in the different doses of paeoniflorin group were improved, and the neuronal edema in the cortical area was alleviated. The activities of SOD, LDH and Na+-K+-ATPase were significantly increased, and the contents of MDA and LD were decreased. CONCLUSION: Therefore, paeoniflorin could alleviate the degree of tissue damage in rats with acute cerebral infarction, inhabit the formation of free radicals in the brain tissue after ischemia, and reduce the degree of lipid peroxidation. Thus, the degree of cell damage was reduced greatly and a protective effect was showed on cerebral ischemia.


Assuntos
Infarto Cerebral/prevenção & controle , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença Aguda , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Infarto Cerebral/metabolismo , Infarto Cerebral/patologia , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Nimodipina/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/metabolismo
20.
Stroke ; 51(2): 659-662, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31856694

RESUMO

Background and Purpose- This study aims to investigate the association between the characteristics of atherosclerotic plaques of middle cerebral artery and recurrent ischemic stroke using magnetic resonance vessel wall imaging. Methods- One hundred and five patients with ischemic stroke attributed to middle cerebral artery plaque underwent high-resolution black-blood magnetic resonance vessel wall imaging. They were divided into group 1, with the first episode of acute stroke (imaging within 4 weeks of stroke, n=44); group 2, with recurrent acute stroke (n=29); and group 3, with chronic stroke (imaging after 3 months of stroke, n=32). Plaque characteristics including plaque area, plaque burden, contrast-enhancement ratio, eccentricity, and degree of stenosis were measured and compared across 3 groups. Association between plaque characteristics and recurrent strokes was investigated by multivariate analysis. Results- Plaque burden was significantly greater in recurrent stroke group than the other 2 groups (median: group 2, 82.7%, versus group 1, 76.3%, and group 3, 73.4%; P=0.001). Patients with acute stroke had higher enhancement ratio than patients with chronic stroke (median: group 1, 1.59, and group 2, 1.90, versus group 3, 1.33; P=0.014). Comparing to first-onset acute stroke patients, recurrent stroke patients were older, more likely with female sex and hypertension, and had higher plaque burden. After adjustment of clinical factors, plaque burden was the only independent imaging feature associated with recurrent stroke (odds ratio, 2.26, per 10% increase [95% CI, 1.03-4.96]; P=0.042). Conclusions- Higher plaque burden of middle cerebral artery identified on magnetic resonance vessel wall imaging is independently associated with recurrent ischemic stroke.


Assuntos
Arteriosclerose Intracraniana/patologia , Angiografia por Ressonância Magnética , Artéria Cerebral Média/patologia , Placa Aterosclerótica/patologia , Acidente Vascular Cerebral/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Infarto Cerebral/complicações , Infarto Cerebral/patologia , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações
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