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1.
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
2.
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
3.
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
4.
BMC Neurol ; 19(1): 279, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718589

RESUMO

BACKGROUND: Cerebral infarction occurs when the arteries to brain are obstructed, and motor impairment contralateral to responsible lesion is commonly recognized. Few studies have profiled the characteristics of cases with ipsilateral motor impairment. We sought to characterize clinical features of patients with motor dysfunction caused by ipsilateral ischemic stroke. METHODS: We retrieved and analyzed the medical data for patients with ipsilateral cerebral infarction. Patients were regarded as having ipsilateral cerebral infarction if motor impairment is ipsilateral to recent stroke lesions. RESULTS: Only 22 patients with unusual ipsilateral cerebral infarction were included in this study. Ipsilateral limb paralysis was observed in all cases, and one case showed central facioplegia. Majority of patients with limb paralysis (90.9%, 20/22) presented with mild muscle strength deficits (MRC grading of 4 or more). Most of the patients (72.7%, 16/22) had a past history of stroke, and previous strokes were contralateral to the side of the recent stroke in 14 out of 16 patients (87.5%). No history of stroke or cerebral injury was identified in seven patients. With aspect of MRI findings, recent infarct lesions of all cases were located along the corticospinal tract. CONCLUSIONS: History of stroke plays an important role in the pathogenesis of ipsilateral motor impairment, and cortical reorganization in the unaffected hemisphere may contribute to the compensation of motor function after stroke. Besides that, some cases with first stroke may be due to impairment of ipsilateral uncrossed corticospinal fibers.


Assuntos
Infarto Cerebral/complicações , Infarto Cerebral/patologia , Lateralidade Funcional/fisiologia , Paralisia/etiologia , Paralisia/fisiopatologia , Adulto , Idoso , Infarto Cerebral/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos Motores/etiologia , Transtornos Motores/fisiopatologia , Neuroimagem , Paralisia/diagnóstico por imagem , Acidente Vascular Cerebral/complicações
5.
Medicine (Baltimore) ; 98(44): e17665, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689779

RESUMO

RATIONALE: Due to the rarity of bilateral cerebral peduncular infarction (BCPI), its symptoms and prognosis are not clear. It is necessary to collect cases of pure cerebral peduncular infarction, explore the etiology and anatomy of midbrain infarction in depth, and develop meaningful tools for explaining clinical symptoms and predicting prognosis of patients. PATIENT CONCERNS: We here provide a case of isolated BCPI with uncommon symptoms of ataxia, dysarthria, sensory disturbance, normal muscular strength, and full eye movements. DIAGNOSES: Diffusion weighted images and apparent diffusion coefficient map of our patient revealed acute and isolated bilateral peduncle cerebrum infarction. INTERVENTIONS: Drugs that could improve circulation and antiplatelet were used in therapy. OUTCOMES: The infarct size was enlarged and new infarction was identified in the splenium of the corpus callosum and pons. The patient developed progressed disorder of consciousness and died at the eleventh day. LESSONS: We inferred that the symptoms of ataxia, dysarthria, sensory disturbance, and mild paresis of the extremities could be prominent features of patients with pure cerebral peduncular infarction. We hypothesize that pure BCPI is also related to severe basilar artery stenosis or occlusion and there is no collateral circulation from PCA. This may explain the corresponding distribution of cerebral peduncular infarction and its poor prognosis. For these reasons, exploring etiology and anatomy of midbrain infarction in depth would have clinical value for predicting symptoms and prognosis.


Assuntos
Infarto Cerebral/fisiopatologia , Pedúnculo Cerebral/fisiopatologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Pedúnculo Cerebral/diagnóstico por imagem , Pedúnculo Cerebral/patologia , Imagem de Difusão por Ressonância Magnética , Humanos , Masculino , Pessoa de Meia-Idade
6.
Rev Cardiovasc Med ; 20(3): 179-186, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601092

RESUMO

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathyis a rare form of inherited cerebral small vessel disease associated with mutations in the high-temperature requirement serine peptidase A1 gene. As of now, only about 50 cases have been reported. In 2012, our group reported a family with a novel mutant of the high-temperature requirement serine peptidase A1 gene in China for the first time. To further explore the molecular pathogenesis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, a recombination mouse model expressed human high-temperature requirement serine peptidase A1 gene mutant identified by our group was generated using the Donor & Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 system and termed the Mut-high-temperature requirement serine peptidase A1 geneL364P mouse model. Results show that Mut-high-temperature requirement serine peptidase A1 geneL364P mice present similar pathological characteristics to patients with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, suggesting that the Mut-high-temperature requirement serine peptidase A1 geneL364P mouse model was generated successfully. Moreover, apoptosis was induced in mouse brain vascular smooth muscle cells derived from Mut-high-temperature requirement serine peptidase A1 geneL364P mice. In summary, the cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy mouse model described in this study will be beneficial to demonstrate the pathological mechanism of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy and provide new therapeutic targets for clinical treatment.


Assuntos
Alopecia/genética , Encéfalo/irrigação sanguínea , Infarto Cerebral/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Leucoencefalopatias/genética , Mutação , Doenças da Coluna Vertebral/genética , Alopecia/enzimologia , Alopecia/patologia , Animais , Apoptose , Células Cultivadas , Infarto Cerebral/enzimologia , Infarto Cerebral/patologia , Predisposição Genética para Doença , Serina Peptidase 1 de Requerimento de Alta Temperatura A/metabolismo , Leucoencefalopatias/enzimologia , Leucoencefalopatias/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/enzimologia , Miócitos de Músculo Liso/patologia , Fenótipo , Doenças da Coluna Vertebral/enzimologia , Doenças da Coluna Vertebral/patologia
7.
Wiad Lek ; 72(9 cz 2): 1851-1853, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622278

RESUMO

Occlusion of artery of Percheron is a rare condition caused by a peculiar anatomic variation in cerebral blood supply, leading to a bilateral thalamic infarction. Strokes in artery of Percheron account for 0.1% to 2% of all cerebral infarctions. Thalamic area is supplied by the arteries arising directly from the P1 segment of the posterior cerebral artery. However, in 1/3 of cases the supply is provided by a single trunk referred to as artery of Percheron (AOP). Early diagnosis of stroke in AOP can be very challenging due to an ambiguous clinical presentation and the absence of neurovisualization findings. This article presents two clinical cases of stroke in artery of Percheron observed at Lviv Emergency Hospital. Different clinical progression of a cerebrovascular accident contrasted with a similar neurovisualization pattern was a distinctive feature in these patients. Taking into consideration the rarity of this condition and a characteristic clinical presentation, these clinical cases were retrospectively analyzed and compared. A stroke in AOP should be suspected in all patients with symptoms of interrupted blood supply in the vertebrobasilar territory. The diagnosis primarily depends on clinical features; patients with paramedian bilateral thalamic lesions may develop sudden problems with consciousness, vertical gaze palsy and memory disorders. Early diagnosis of this condition allows for more effective therapeutic interventions and improves patient prognosis.


Assuntos
Infarto Cerebral/diagnóstico , Artéria Cerebral Posterior/patologia , Acidente Vascular Cerebral/diagnóstico , Infarto Cerebral/patologia , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/patologia , Tálamo
9.
Zhonghua Nei Ke Za Zhi ; 58(6): 449-452, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31159525

RESUMO

To explore the clinical significance of C1q tumor necrosis factor-related protein-9 (CTRP9) in patients with cerebral infarction. Our data showed that the serum CTRP9 was significantly lower than that of control group, especially in patients with large artery atherosclerotic cerebral infarction. CTRP9 was first decreased and even lower from day 4 to day 10, then gradually elevated. Logistic regression analysis suggested that high CTRP9 level was a protective factor for cerebral infarction. Thus, CTRP9 could be a factor for further classification of cerebral infarction and provides a potential option for disease prevention and treatment.


Assuntos
Adiponectina/biossíntese , Infarto Cerebral/metabolismo , Glicoproteínas/biossíntese , Adiponectina/sangue , Infarto Cerebral/patologia , Glicoproteínas/sangue , Humanos , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral
10.
J Clin Lab Anal ; 33(6): e22891, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30955225

RESUMO

BACKGROUND: Acute cerebral infarction (ACI) is seriously harmful to human health worldwide. However, at present, the risk of disease onset is still not accurately predicted for some people. METHODS: Five hundred and nineteen patients with ACI and 300 healthy controls were included in this study. We divided the patients into three groups according to the results of cervical artery contrast-enhanced ultrasound. Ninety-five patients were in the CAS without plaque group, 108 patients were in the stable plaque group, and 316 patients were in the unstable plaque group. TC, TG, HDL-C, LDL-C, and sdLDL-C were measured in all subjects. RESULTS: The level of small dense low-density lipoprotein cholesterol (sdLDL-C) in the ACI group was significantly higher than that in the control group (P < 0.001). Logistic regression analysis showed that sdLDL-C was an independent risk factor for ACI (OR = 1.067, 95% CI: 1.041-1.093, P < 0.001); serum sdLDL-C was significantly higher in the unstable plaque group than in the stable plaque group and plaque-free group (P < 0.05, P < 0.001); serum sdLDL-C was also higher in the stable plaque group than the plaque-free group (P < 0.001). Logistic regression analysis showed that sdLDL-C was an independent risk factor for unstable carotid plaques (OR = 1.053, 95% CI: 1.038-1.068, P < 0.001); Spearman correlation analysis showed that sdLDL-C test results were positively correlated with carotid plaque stability (r = 0.363, P < 0.001). CONCLUSION: Small dense low-density lipoprotein cholesterol is an independent risk factor for the onset of ACI and may be an early serum marker for this disease.


Assuntos
Infarto Cerebral/patologia , LDL-Colesterol/sangue , Placa Aterosclerótica/patologia , Idoso , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , Estudos de Casos e Controles , Infarto Cerebral/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico por imagem , Curva ROC , Triglicerídeos/sangue
11.
World Neurosurg ; 127: e873-e880, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30954745

RESUMO

BACKGROUND: Corpus callosum (CC) infarction has been reported to be rare because of the rich blood supply in the CC. The pathophysiology of CC infarction associated with acute hydrocephalus is unknown. The aim of the present study was to clarify the characteristics and mechanism of CC infarction associated with acute noncommunicating hydrocephalus (ANCH). METHODS: We reviewed clinical the data from all patients who had undergone surgical intervention for ANCH at Chiba University Hospital from January 2008 to March 2018. Patients with vascular lesions, a history of hydrocephalus, and lacking magnetic resonance imaging studies were excluded. The clinical, surgical, and radiological parameters were obtained retrospectively for pathophysiological analysis. RESULTS: A total of 23 patients with ANCH who had undergone surgical intervention and had met the inclusion criteria were included in the present study. Of the 23 patients, 6 (23%) had developed CC infarction. All CC infarctions were located in the splenium. Although no clinical or surgical features were associated with splenial infarction, the radiological parameters of lateral ventricle enlargement and a narrower callosal angle at the posterior commissure and the foramen of Monro were significantly associated with splenial infarction. CONCLUSION: The present study has presented evidence that increased intraventricular pressure by ANCH applied transversely in the splenium will directly induce compression of the superior branch of the posterior callosal artery and pericallosal pial plexus, resulting in splenium-specific infarction in patients with ANCH.


Assuntos
Corpo Caloso/patologia , Corpo Caloso/cirurgia , Hidrocefalia/patologia , Hidrocefalia/cirurgia , Doença Aguda , Adolescente , Adulto , Idoso , Artérias/patologia , Artérias/cirurgia , Infarto Cerebral/patologia , Infarto Cerebral/cirurgia , Criança , Pré-Escolar , Corpo Caloso/irrigação sanguínea , Feminino , Humanos , Infarto/patologia , Infarto/cirurgia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Radiologia/métodos , Adulto Jovem
12.
Brain Dev ; 41(8): 699-705, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31003833

RESUMO

PURPOSE: To identify the frequency of epilepsy and whether the association of epilepsy with clinical and neuroimaging findings in children with presumed perinatal arterial ischemic stroke (PPAIS). METHODS: We performed a retrospective analysis of 37 children with PPAIS followed-up at a tertiary referral center between January 1, 2000, and October 31, 2016. Clinical data including demographic features, age at onset of symptoms and seizures, initial clinical presentation, epilepsy features, used antiepileptic drugs, and thrombophilia screening results were abstracted from medical records. Brain magnetic resonance imaging scans were assessed for infarct laterality, location and affected brain regions. RESULTS: The median age of the patients was 12 years (range 2-17.9 years) at last assessment. The initial symptom of PPAIS was early hand preference in 33 children (89%) and seizure in 4 children (11%). A total of 20 children (54%) developed epilepsy at a median age of 0.9 years. There were two peaks of epilepsy onset in infancy and adolescence. Fifteen children (41%) had focal epilepsy and 5 children (14%) had epileptic spasms. Twelve out of 20 children (60%) with epilepsy had drug resistant epilepsy. Cortical involvement was a statistically significant predictor of epilepsy (p = 0.021, relative risk 4.4, 95% confidence interval 0.7-27.7). CONCLUSION: More than half of the children with PPAIS suffered from epilepsy during childhood, of whom developed drug resistant epilepsy in majority. Children with cortical lesion may have a higher risk to develop epilepsy.


Assuntos
Isquemia Encefálica/complicações , Epilepsia/epidemiologia , Acidente Vascular Cerebral/complicações , Adolescente , Anticonvulsivantes/uso terapêutico , Encéfalo/patologia , Isquemia Encefálica/patologia , Infarto Cerebral/patologia , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia/tratamento farmacológico , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Assistência Perinatal , Gravidez , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Espasmo/patologia , Espasmos Infantis/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Turquia/epidemiologia
13.
Neuroreport ; 30(6): 428-433, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30829959

RESUMO

Ischemic stroke is a common life-threatening disease. Epidemiological studies have shown that chronic periodontitis is closely related to ischemic stroke. However, it remains unknown whether periodontitis plays a direct role in the injury of cerebral ischemia. To explore the role of chronic periodontitis in the development process of ischemic stroke, we combined two mouse models: experimental periodontitis induced by a periodontal injection of lipopolysaccharide and ischemic stroke induced by the photothrombotic method. Alveolar bone loss and inflammatory infiltration of the periodontal tissue were found in the mice with experimental periodontitis. Periodontitis significantly increased the infarction volume, and numbers of activated microglia and astrocytes. Furthermore, an increased expression of nod-like receptor protein 3 inflammasome and interleukin-1ß was detected in the peri-infarct region. We drew a conclusion that chronic periodontitis exacerbated ischemic stroke by increasing the activation of microglia/astrocytes and the expression of nod-like receptor protein 3 inflammasome and interleukin-1ß. This suggested that chronic periodontitis played a role in ischemic brain injury directly through exacerbating the inflammation of the damaged brain.


Assuntos
Infarto Cerebral/patologia , Inflamação/patologia , Periodontite/patologia , Animais , Infarto Cerebral/imunologia , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Periodontite/complicações , Periodontite/imunologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia
14.
J Int Med Res ; 47(3): 1373-1377, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30760064

RESUMO

Large artery atherosclerosis and cardioembolism are the two major subtypes of ischemic stroke. We herein describe a 75-year-old man with acute complete cerebral infarction in the typical territories of the bilateral anterior cerebral artery (ACA) and left middle cerebral artery. Brain magnetic resonance angiography showed that the right A1 segment of the ACA was affected by severe arteriosclerosis and that the right ACA other than the A1 segment was compensated by the left ACA through the anterior communicating artery. Acute cardioembolism only occluded the left anterior circulation but simultaneously blocked the right ACA due to decompensation. We presume that the bilateral cerebral infarctions were caused by chronic atherosclerosis and acute cardioembolism.


Assuntos
Arteriosclerose/patologia , Infarto Cerebral/patologia , Idoso , Arteriosclerose/complicações , Arteriosclerose/diagnóstico por imagem , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico por imagem , Humanos , Angiografia por Ressonância Magnética , Masculino , Prognóstico , Tomografia Computadorizada por Raios X
15.
Neurology ; 92(9): e933-e943, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30700595

RESUMO

OBJECTIVE: We sought to determine the underlying mechanism for altered white matter diffusion tensor imaging (DTI) measures at the histopathologic level in patients with cerebral amyloid angiopathy (CAA). METHODS: Formalin-fixed intact hemispheres from 9 CAA cases and 2 elderly controls were scanned at 3-tesla MRI, including a diffusion-weighted sequence. DTI measures (i.e., fractional anisotropy [FA] and mean diffusivity [MD]) and histopathology measures were obtained from 2 tracts: the anterior thalamic radiation and inferior longitudinal fasciculus. RESULTS: FA was reduced in both tracts and MD was increased in cases with CAA compared to controls. Regional FA was significantly correlated with tissue rarefaction, myelin density, axonal density, and white matter microinfarcts. MD correlated significantly with tissue rarefaction, myelin density, and white matter microinfarcts, but not axonal density. FA and MD did not correlate with oligodendrocytes, astrocytes, or gliosis. Multivariate analysis revealed that tissue rarefaction (ß = -0.32 ± 0.12, p = 0.009) and axonal density (ß = 0.25 ± 0.12, p = 0.04) were both independently associated with FA, whereas myelin density was independently associated with MD (ß = -0.32 ± 0.12, p = 0.013). Finally, we found an association between increased MD in the frontal white matter and CAA severity in the frontal cortex (p = 0.035). CONCLUSIONS: These results suggest that overall tissue loss, and in particular axonal and myelin loss, are major components underlying CAA-related alterations in DTI properties observed in living patients. The findings allow for a more mechanistic interpretation of DTI parameters in small vessel disease and for mechanism-based selection of candidate treatments to prevent vascular cognitive impairment.


Assuntos
Axônios/patologia , Angiopatia Amiloide Cerebral/patologia , Infarto Cerebral/patologia , Fibras Nervosas Mielinizadas/patologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Estudos de Casos e Controles , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem
16.
Medicina (Kaunas) ; 55(2)2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30720741

RESUMO

BACKGROUND AND OBJECTIVES: Cranial magnetic resonance imaging findings of patients considered to be cryptogenic stroke may be useful in determining the clinical and prognostic significance of arrhythmias, such as atrial premature beats and atrial run attacks, that are frequently encountered in rhythm Holter analysis. This study was conducted to investigate the relationship between short atrial runs and frequent premature atrial contractions detected in Holter monitors and infarct distributions in cranial magnetic resonance imaging of patients diagnosed with cryptogenic stroke. MATERIALS AND METHODS: We enrolled the patients with acute ischemic stroke whose etiology were undetermined. We divided the patients in two groups according to diffusion-weighted magnetic resonance imaging as single or multiple vascular territory acute infarcts. The demographic, clinical, laboratory, echocardiographic, and rhythm Holter analyses were compared. RESULTS: The study investigated 106 patients diagnosed with cryptogenic stroke. Acute cerebral infarctions were detected in 31% of the investigated patients in multiple territories and in 69% in a single territory. In multivariate logistic regression analysis, the total premature atrial contraction count (OR = 1.002, 95% CI: 1.001⁻1.004, p = 0.001) and short atrial run count (OR = 1.086, 95% CI: 1.021⁻1.155, p = 0.008) were found as independent variables that could distinguish between infarctions in a single or in multiple vascular territories. CONCLUSIONS: Rhythm Holter monitoring of patients with infarcts detected in multiple vascular territories showed significantly higher premature atrial contractions and short atrial run attacks. More effort should be devoted to the identification of cardioembolic etiology in cryptogenic stroke patients with concurrent acute infarcts in the multiple vascular territories of the brain.


Assuntos
Infarto Cerebral/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Eletrocardiografia Ambulatorial , Fatores Etários , Idoso , Fibrilação Atrial/complicações , Complexos Atriais Prematuros/fisiopatologia , Proteína C-Reativa/análise , Infarto Cerebral/sangue , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Coleta de Dados , Feminino , Hemoglobinas/análise , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
17.
JAMA Neurol ; 76(2): 194-202, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30615038

RESUMO

Importance: The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke. Objective: To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke. Design, Setting, and Participants: Patient data from 7 randomized multicenter trials were pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography or magnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017. Main Outcome and Measure: The 90-day functional outcome via the modified Rankin Scale (mRS). Results: Among 1665 patients, the median (interquartile range [IQR]) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median [IQR] FIV, 33 [11-99] vs 51 [18-134] mL; P = .007) and lower mRS scores at 90 days (median [IQR] score, 3 [1-4] vs 4 [2-5]). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P < .001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P < .001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome. Conclusions and Relevance: In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.


Assuntos
Isquemia Encefálica/patologia , Isquemia Encefálica/terapia , Procedimentos Endovasculares/estatística & dados numéricos , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapia , Idoso , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia
18.
Artif Cells Nanomed Biotechnol ; 47(1): 192-200, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30663409

RESUMO

After cerebral infarction, the regeneration of microvascular played an important role in the recovery. Ginsenoside Rg1 (Rg1) had good effects on promoting angiogenesis and neuro-protection in cerebral infarction treatment. However, the blood-brain barrier (BBB) restricted Rg1 to enter into cerebral tissue. Transferrin receptor (TfR) was over-expressed in the BBB. In this study, we fabricated a TfR targeting nano-carrier (PATRC) to penetrate the BBB for treatment of cerebral infarction. A TfR targeted peptide was conjugated with the nano-carrier wrapped hydrophobic Rg1. The nanoscale size (132 ± 12 nm), polydispersity index (PDI =0.29) and the zeta potential (-38mv) were tested with dynamic light scattering optical system. Surface morphology (ellipse, mean diameter 122 ± 26 nm) was detected by transmission electron microscope (TEM). PATRC implement cell targeting ability on rat brain microvascular endothelial cells RBE4 in vitro detected by immunofluorescence and flow cytometry methods. Comparing with Rg1 threated group, the PATRC exhibited more prominent ability on the tube formation ability (p < .05) in vitro. Comparing with the Rg1 treated group, PATRC penetrated BBB in vivo detected by HPLC, decreased the brain infarction volume tested with TTC staining and promoted regeneration of microvascular in infarction zone detected by CD31 immunofluorescence. PATRC has great potentiality for wide application in clinic.


Assuntos
Infarto Cerebral/tratamento farmacológico , Portadores de Fármacos/química , Terapia de Alvo Molecular , Nanoestruturas/química , Receptores da Transferrina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Hipóxia Celular/efeitos dos fármacos , Infarto Cerebral/metabolismo , Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologia , Quitosana/química , Portadores de Fármacos/metabolismo , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Masculino , Maleimidas/química , Microvasos/efeitos dos fármacos , Microvasos/fisiopatologia , Ácido Poliglutâmico/química , Ratos , Ratos Sprague-Dawley
19.
Med Sci Law ; 59(1): 17-19, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30674223

RESUMO

Traumatic dissection of the carotid arteries is a rare cause of delayed death due to hanging. We report a case of delayed death two and a half months following attempted suicide by hanging where the patient was able to talk after being released from neck compression. The cause of death was aspiration pneumonia due to cerebral infarction secondary to traumatic dissection of the left common carotid artery due to attempted suicide by hanging. Carotid artery injuries should be examined in patients who were able to talk after an unsuccessful suicide attempt by hanging but who later died.


Assuntos
Lesões das Artérias Carótidas/etiologia , Artéria Carótida Primitiva/patologia , Lesões do Pescoço/complicações , Pneumonia Aspirativa/etiologia , Tentativa de Suicídio , Idoso , Lesões das Artérias Carótidas/patologia , Infarto Cerebral/complicações , Infarto Cerebral/patologia , Humanos , Masculino , Fatores de Tempo
20.
Nat Commun ; 10(1): 187, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30643122

RESUMO

Pharmacologic activation of stress-responsive signaling pathways provides a promising approach for ameliorating imbalances in proteostasis associated with diverse diseases. However, this approach has not been employed in vivo. Here we show, using a mouse model of myocardial ischemia/reperfusion, that selective pharmacologic activation of the ATF6 arm of the unfolded protein response (UPR) during reperfusion, a typical clinical intervention point after myocardial infarction, transcriptionally reprograms proteostasis, ameliorates damage and preserves heart function. These effects were lost upon cardiac myocyte-specific Atf6 deletion in the heart, demonstrating the critical role played by ATF6 in mediating pharmacologically activated proteostasis-based protection of the heart. Pharmacological activation of ATF6 is also protective in renal and cerebral ischemia/reperfusion models, demonstrating its widespread utility. Thus, pharmacologic activation of ATF6 represents a proteostasis-based therapeutic strategy for ameliorating ischemia/reperfusion damage, underscoring its unique translational potential for treating a wide range of pathologies caused by imbalanced proteostasis.


Assuntos
Fator 6 Ativador da Transcrição/metabolismo , Infarto Cerebral/prevenção & controle , Nefropatias/prevenção & controle , Infarto do Miocárdio/prevenção & controle , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Fator 6 Ativador da Transcrição/genética , Animais , Animais Recém-Nascidos , Células Cultivadas , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Modelos Animais de Doenças , Retículo Endoplasmático/metabolismo , Feminino , Ventrículos do Coração/patologia , Humanos , Rim/irrigação sanguínea , Rim/patologia , Nefropatias/etiologia , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Miócitos Cardíacos , Cultura Primária de Células , Substâncias Protetoras/uso terapêutico , Proteostase/efeitos dos fármacos , Ratos , Traumatismo por Reperfusão/etiologia , Resultado do Tratamento , Resposta a Proteínas não Dobradas/efeitos dos fármacos
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