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1.
J Stroke Cerebrovasc Dis ; 29(2): 104529, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31806455

RESUMO

BACKGROUND: Controversial evidence suggests that right insular stroke may be associated with worse outcomes compared to the left insular ischemic lesion. OBJECTIVES: We investigated whether lateralization of insular stroke is associated with early and late outcome in terms of in-hospital complications, stroke recurrence, cardiovascular events, and death. METHODS: Data were prospectively collected from the Athens Stroke Registry. Insular cortex involvement was identified based on brain CT scans or MRI images. Patients were followed up prospectively at 1, 3, 6 months after hospital discharge and yearly thereafter up to 5-years or until death. The assessed outcomes were in-hospital complications, functional outcome assessed by the modified Rankin Scale, stroke recurrence, cardiovascular events, and death. Cox-regression analysis was performed to estimate the cumulative probability of each outcome according to the lateralization of insular strokes. RESULTS: Among the 1212 patients, 650 had left insular stroke involvement and 562 had right. New onset of in-hospital atrial fibrillation was similar between right and left insular strokes (11.6% versus 12.9%, P = .484). During the 5-year follow-up sudden death occurred in 21 (3.7%) patients with right insular compared to 30 (4.6%) with left insular stroke (P = .476). There was no difference between left and right insular strokes regarding mortality (adjusted odds ratio [OR]: .92, 95% confidence interval [CI]: .80-1.06), stroke recurrence (4.3% versus 4.9%; adjusted OR: .81 95% CI: .58-1.13), cardiovascular events, and sudden death (adjusted OR: .99, 95% CI: .76-1.29) and on death and dependency (adjusted OR: .88, 95% CI: .75-1.02) during a 5-year follow up. CONCLUSIONS: Lateralization of insular ischemic stroke involvement is not associated with stroke outcomes.


Assuntos
Isquemia Encefálica/fisiopatologia , Córtex Cerebral/irrigação sanguínea , Lateralidade Funcional , Acidente Vascular Cerebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Isquemia Encefálica/terapia , Causas de Morte , Circulação Cerebrovascular , Progressão da Doença , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Recidiva , Sistema de Registros , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapia , Fatores de Tempo
2.
Opt Lett ; 44(20): 5037-5040, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613257

RESUMO

We report the use of an electrically tunable lens (ETL) in a 1.3 µm spectral-domain optical coherence tomography (SD-OCT) system to overcome the depth of focus (DOF) limitation in conventional OCT systems for OCT angiography (OCTA) in a mouse cerebral cortex. The ETL provides fast and dynamic control of the axial focus of the probe beam along the entire range of the mouse cortex, upon which we performed cerebral blood flow imaging of all cortical layers by stitching the OCTA images automatically captured at six focal depths. Capillary vasculature and axial blood flow velocity were revealed in distinctive cortical layers and, for the first time, to the best of our knowledge, in white matter. The results have shown the system capability to conveniently investigate the hemodynamics in deep cortical layers in the mouse brain. More importantly, the compact integration of an ETL will benefit the future design of handheld or intra-cavity OCT probes for a wide range of applications in research and clinical fields.


Assuntos
Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/diagnóstico por imagem , Circulação Cerebrovascular , Eletricidade , Tomografia de Coerência Óptica/instrumentação , Animais , Lentes , Camundongos
3.
J Stroke Cerebrovasc Dis ; 28(11): 104308, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31416760

RESUMO

Stroke involving some areas of the cerebral hemisphere, such as insula, amygdala, and lateral hypothalamus, may cause changes in autonomic control of cardiac function. A 58-year-old woman presented to the emergency department for acute onset of left facial-brachial-crural hemiparesis and dysarthria. A brain CT scan showed subacute ischemic lesion with hemorrhagic infarction in right insular-rolandic cortex. Over the next few days ECG showed severe bradycardia with elongation of QTc, significative pauses (5 seconds), runs of nonsustained ventricular tachycardia and torsades de pointes. Drug induced and other several possible causes of elongation of QT and bradycardia such as hypokalemia, a history of heart failure, and structural heart disease were ruled out. The case confirms that insular cortex plays a major role in stroke-induced cardiovascular changes.


Assuntos
Córtex Cerebral/irrigação sanguínea , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Síndrome do QT Longo/etiologia , Acidente Vascular Cerebral/complicações , Torsades de Pointes/etiologia , Potenciais de Ação , Bradicardia/etiologia , Bradicardia/fisiopatologia , Estimulação Cardíaca Artificial , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Síndrome do QT Longo/terapia , Pessoa de Meia-Idade , Marca-Passo Artificial , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Torsades de Pointes/diagnóstico , Torsades de Pointes/fisiopatologia , Torsades de Pointes/terapia , Resultado do Tratamento
4.
Sheng Li Xue Bao ; 71(4): 581-587, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440755

RESUMO

The purpose of this study was to establish a method to record the dynamic process of vascular regeneration and remodeling in rat cerebral ischemic regions. An animal brain window model was established to continuously observe the changes of rat cortical vascular ischemia in vivo, and the model of cerebral ischemia was established by photochemical embolization. Optical coherence tomography (OCT) was performed to record the formation of vascular blockage and the injury and regeneration of small vessels during cerebral ischemia recovery. The results showed that 30 min of laser irradiation could completely block the cortical vessels in rats. Within 24-48 h after ischemia, the degree of brain injury was the greatest, and the number of blood vessels in the ischemic region reached the minimum. Then the blocked blood vessels began to be dredged, and the small blood vessels around the ischemic area began to regenerate. Small blood vessels in the superficial/deep layers of the cortex disappeared significantly after laser irradiation. During 10 d after ischemia, the blocked blood vessels were gradually dredged and recovered. On the 10th day after laser irradiation, a large number of neovascularization appeared in the superficial layer of cortex, but the deep vessels did not recover. These results indicate that the method established in this study can observe the changes of blood vessel in cerebral ischemic region continuously, which lays a foundation for further quantitative study on the dynamics of embolized blood vessels and peripheral capillaries during the recovery of cerebral ischemia.


Assuntos
Isquemia Encefálica , Encéfalo/irrigação sanguínea , Córtex Cerebral/irrigação sanguínea , Regeneração , Animais , Ratos
5.
Stroke ; 50(7): 1727-1733, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31159702

RESUMO

Background and Purpose- Hematoma location within the cerebellum may help identify the dominant small vessel disease type (cerebral amyloid angiopathy [CAA] versus nonamyloid small vessel disease). However, it is unknown whether this holds true for cerebral microbleeds (CMBs) within the cerebellum. We tested the hypothesis that cerebellar CMBs restricted to the cortex and vermis (defined as superficial regions) are associated with clinically diagnosed and pathology-verified CAA. Methods- Three hundred and seven consecutive spontaneous intracerebral hemorrhage (ICH) patients with a baseline magnetic resonance imaging that included susceptibility-weighted imaging or angiography were enrolled. Using a topographical template, cerebellar CMB patterns were defined as strictly superficial versus deep (cerebellar gray nuclei and white matter) or mixed (both regions involved). Thirty-six ICH patients with cerebellar CMBs and neuropathology data available were evaluated for the presence of CAA. Results- One hundred and thirty-five (44%) ICH patients had CMBs in the cerebellum. In the patient group with cerebellar CMBs, 85 (63%) showed a superficial pattern, and 50 (37%) had a deep/mixed pattern. Strictly superficial cerebellar CMBs were independently associated with a supratentorial pattern of probable CAA-ICH according to the Boston criteria (odds ratio, 1.6; CI, 1.03-2.5) and deep/mixed cerebellar CMBs with a pattern of deep/mixed ICH (odds ratio, 1.8; CI, 1.2-2.7). Pathologically verified CAA was present in 23 of 24 (96%) patients with superficial cerebellar CMBs versus 3 of 12 (25%) patients with deep/mixed cerebellar CMBs ( P<0.001). Conclusions- In ICH patients, cerebellar CMBs are relatively common and often restricted to superficial regions. A strictly superficial distribution of cerebellar CMBs is associated with clinically diagnosed and pathologically verified CAA.


Assuntos
Angiopatia Amiloide Cerebral/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Imagem por Ressonância Magnética , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Angiopatia Amiloide Cerebral/fisiopatologia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/fisiopatologia , Hemorragia Cerebral/fisiopatologia , Feminino , Substância Cinzenta/irrigação sanguínea , Substância Cinzenta/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Substância Branca/irrigação sanguínea , Substância Branca/fisiopatologia
6.
Cerebrovasc Dis ; 47(3-4): 178-187, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31121577

RESUMO

OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard surgical management for adult moyamoya disease (MMD) patients, but local cerebral hyperperfusion (CHP) and cerebral ischemia are potential complications of this procedure. Recent hemodynamic analysis of the acute stage after revascularization surgery for MMD revealed a more complex and unique pathophysiological condition, the so-called "watershed shift (WS) phenomenon," which is defined as a paradoxical decrease in the cerebral blood flow (CBF) at the adjacent cortex near the site of local CHP. The objective of this study was to clarify the exact incidence, clinical presentation, and risk factors of the WS phenomenon after direct revascularization surgery for adult MMD. PATIENTS AND METHODS: Among 74 patients with MMD undergoing STA-MCA anastomosis for 78 affected hemispheres, 60 adult patients comprising 64 hemispheres underwent serial quantitative CBF analysis by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography after revascularization surgery. The local CBF was quantitatively measured at the site of anastomosis and the adjacent cortex before surgery, as well as on 1 and 7 days after surgery. Then, we investigated the incidence, clinical presentation, and risk factors of the WS phenomenon. RESULTS: The WS phenomenon was evident in 7 patients (7/64 hemispheres; 10.9%) after STA-MCA anastomosis for adult MMD. None of the patients developed neurological deterioration due to the WS phenomenon, but 1 patient developed reversible ischemic change on diffusion-weighted imaging at the site of the WS phenomenon. Multivariate analysis revealed that a lower preoperative CBF value was significantly associated with the occurrence of the WS phenomenon (20.3 ± 7.70 mL/100 g/min in WS-positive group vs. 31.7 ± 8.81 mL/100 g/min in WS-negative group, p= 1.1 × 10-2). CONCLUSIONS: The incidence of the WS phenomenon was as high as 10.9% after STA-MCA anastomosis for adult MMD. The clinical outcome of the WS phenomenon is generally favorable, but there is a potential risk for perioperative cerebral infarction. Thus, we recommend routine CBF measurement in the acute stage after revascularization surgery for adult MMD to avoid surgical complications, such as local CHP and cerebral ischemia, caused by the WS phenomenon. Concomitant detection of the WS phenomenon with local CHP is clinically important because blood pressure reduction to counteract local CHP may have to be avoided in the presence of the WS phenomenon.


Assuntos
Córtex Cerebral/irrigação sanguínea , Revascularização Cerebral/efeitos adversos , Circulação Cerebrovascular , Artéria Cerebral Média/cirurgia , Doença de Moyamoya/cirurgia , Complicações Pós-Operatórias/epidemiologia , Artérias Temporais/cirurgia , Adolescente , Adulto , Idoso , Anastomose Cirúrgica/efeitos adversos , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/fisiopatologia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/fisiopatologia , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Fatores de Risco , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/fisiopatologia , Resultado do Tratamento , Adulto Jovem
7.
J Biomed Sci ; 26(1): 36, 2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31078140

RESUMO

BACKGROUND: Vascular dementia is the second dementing illness after Alzheimer's disease and caused by reduced blood flow to the brain, and affects cognitive abilities. Our previous study found that auricular electrical stimulation (ES) improved motor and learning impairment, and this phenomenon related with nicotinic acetylcholine receptor (nAChR) expressed cells. However, the underlying mechanism was not clear. In the present study, we investigated the effects of auricular ES on cortical blood flow (CBF) and acetylcholine (ACh) - nAChRs expressed cells. METHODS: Vascular dementia rat animal model was established by permanent occlusions of common carotid arteries with 6-0 nylon suture filament. At 21 day after surgery, motor impairment was confirmed by rotarod test. 15-Hz auricular ES were applied to the ears for 20 min and CBF was recorded at the mean time. The brains were immediately dissected for immunohistochemical stain and western blot analysis. RESULTS: Our results showed that 15-Hz auricular ES rapidly elevated CBF in the middle cerebral artery. The numbers of nAChR α4 immuno-positive cells and western blot levels were significally increased by 15-Hz auricular ES in the hippocampal CA2 output cortex. The numbers of choline acetyltransferase (ChAT) - a key enzyme for biosynthesis of ACh - immuno-positive cells and western blot levels had no significant differences. CONCLUSIONS: The present data suggested that the 15-Hz auricular ES for 20 min rapidly elevated cortical blood flow, promoted the expression of nAChR α4, and would be beneficial for the treatment of Alzheimer type and vascular type dementia.


Assuntos
Córtex Cerebral/irrigação sanguínea , Colina O-Acetiltransferase/genética , Orelha/fisiologia , Habenula/fisiologia , Hipocampo/fisiologia , Receptores Nicotínicos/genética , Animais , Western Blotting , Circulação Cerebrovascular , Colina O-Acetiltransferase/metabolismo , Modelos Animais de Doenças , Estimulação Elétrica , Expressão Gênica , Imuno-Histoquímica , Isquemia/etiologia , Fluxometria por Laser-Doppler , Masculino , Ratos , Ratos Wistar , Receptores Nicotínicos/metabolismo
8.
Interv Neuroradiol ; 25(3): 322-329, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31138039

RESUMO

We present a case of a novel restrictive cerebral venopathy in a child, consisting of a bilateral network of small to medium cortical veins without evidence of arteriovenous shunting, absence of the deep venous system, venous ischemia, elevated intracranial pressure, and intracranial calcifications. The condition is unlike other diseases characterized by networks of small veins, including cerebral proliferative angiopathy, Sturge-Weber syndrome, or developmental venous anomaly. While this case may be the result of an anatomic variation leading to the congenital absence of or early occlusion of the deep venous system, the insidious nature over many years argues against this. The absence of large cortical veins suggests a congenital abnormality of the venous structure. The child's presentation with a seizure-like event followed by protracted hemiparesis is consistent with venous ischemia. We propose that this is likely to represent a new clinicopathological entity.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Veias Cerebrais/diagnóstico por imagem , Transtornos Cerebrovasculares/diagnóstico por imagem , Adolescente , Isquemia Encefálica/etiologia , Córtex Cerebral/irrigação sanguínea , Paralisia Cerebral/complicações , Transtornos Cerebrovasculares/complicações , Humanos , Imagem por Ressonância Magnética , Masculino , Exame Neurológico , Paresia/etiologia , Convulsões/etiologia , Tomografia Computadorizada por Raios X , Derivação Ventriculoperitoneal
9.
Int J Mol Sci ; 20(10)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091708

RESUMO

We performed a three-dimensional (3D) analysis of the microvascular network of the cerebral cortex of twitcher mice (an authentic model of Krabbe disease) using a restricted set of indexes that are able to describe the arrangement of the microvascular tree in CD31-stained sections. We obtained a near-linear graphical "fingerprint" of the microangioarchitecture of wild-type and twitcher animals that describes the amounts, spatial dispersion, and spatial relationships of adjacent classes of caliber-filtered microvessels. We observed significant alterations of the microangioarchitecture of the cerebral cortex of twitcher mice, whereas no alterations occur in renal microvessels, which is keeping with the observation that kidney is an organ that is not affected by the disease. This approach may represent an important starting point for the study of the microvascular changes that occur in the central nervous system (CNS) under different physiopathological conditions.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imagem Tridimensional/métodos , Leucodistrofia de Células Globoides/diagnóstico por imagem , Microvasos/diagnóstico por imagem , Animais , Córtex Cerebral/irrigação sanguínea , Camundongos , Microscopia Confocal/métodos
10.
Neurosci Lett ; 704: 133-140, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-30954605

RESUMO

Alzheimer's disease (AD) is the most common type of dementia in aging adults. Increasing evidence has revealed that vascular risk factors influence the midlife development of AD and that diet-induced obesity accelerates tau phosphorylation in tau transgenic mice and increases the level of serum leptin receptor (leptin-R). Leptin-R is upregulated in the peri-infarct cortices after acute cerebral ischemia. Leptin may be protective against the development of AD as it can inactivate GSK-3ß through the phosphorylation of Ser-9, leading to the reduction of tau phosphorylation. Using tau transgenic mice, the present study examined whether chronic cerebral hypoperfusion affects leptin-R signaling and tau phosphorylation. Eight-month-old tau transgenic mice (T44) overexpressing the shortest human tau isoform were subjected to chronic cerebral hypoperfusion with bilateral common carotid artery stenosis (BCAS) using microcoils or sham surgery. Their brains were analyzed four weeks later to evaluate the expression of phosphorylated tau and leptin-R via immunohistochemistry and Western blot analysis. In addition, expression of leptin-R was examined in the rat primary astrocyte cultures subjected to prolonged chemical hypoxic stress, as well as in autopsied brains. BCAS upregulated leptin-R expression and promoted the expression of phosphorylated tau in T44 Tg mice. In primary astrocyte cultures, leptin-R was upregulated under hypoxic conditions via the phosphorylated AKT/pAKT pathway, possibly suppressing the expression of caspase 3. Leptin-R was also strongly expressed in autopsied brains with AD and cerebrovascular diseases. These results collectively indicate that chronic cerebral hypoperfusion promotes leptin-R signaling and tau phosphorylation.


Assuntos
Astrócitos/metabolismo , Isquemia Encefálica/metabolismo , Córtex Cerebral/metabolismo , Receptores para Leptina/metabolismo , Proteínas tau/metabolismo , Animais , Isquemia Encefálica/etiologia , Estenose das Carótidas/complicações , Córtex Cerebral/irrigação sanguínea , Masculino , Camundongos Transgênicos , Fosforilação , Regulação para Cima
11.
Methods Mol Biol ; 1947: 377-387, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30969429

RESUMO

A large body of evidence suggests that G protein-coupled receptors (GPCRs) play an important role in the regulation of peripheral vascular reactivity. Meanwhile, the extent of GPCR influence on the regulation of brain vascular reactivity, or cerebral blood flow (CBF), has yet to be fully appreciated. This is of physiological importance as the modulation of CBF depends on an intricate interplay between neurons, astrocytes, pericytes, and endothelial cells, all of which partaking in the formation of a functional entity referred to as the neurovascular unit (NVU). The NVU is the anatomical substrate of neurovascular coupling (NVC) mechanisms, whereby increased neuronal activity leads to increased blood flow to accommodate energy, oxygen, and nutrients demands. In light of growing evidence showing impaired NVC in several neurological disorders, and the fact that GPCRs represent the most important targets of FDA-approved drugs, it is of utmost importance to use experimental approaches to study GPCR-induced regulation of NVC for the future development of pharmaceutical compounds that could normalize CBF function. Herein, we describe a minimally invasive approach called laser Doppler flowmetry (LDF) that, when used in combination with a whisker stimulation paradigm in rodents, allows gauging blood perfusion in activated cerebral cortex. We comprehensively explain the surgical procedure and data acquisition in mice, and discussed about important experimental considerations for the study of CBF regulation by GPCRs using pharmacological agents.


Assuntos
Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular , Fluxometria por Laser-Doppler/métodos , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Camundongos , Ratos
12.
PLoS One ; 14(3): e0213508, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870435

RESUMO

During experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis associated with blood-brain barrier (BBB) disruption, oligodendrocyte precursor cells (OPCs) overexpress proteoglycan nerve/glial antigen 2 (NG2), proliferate, and make contacts with the microvessel wall. To explore whether OPCs may actually be recruited within the neurovascular unit (NVU), de facto intervening in its cellular and molecular composition, we quantified by immunoconfocal morphometry the presence of OPCs in contact with brain microvessels, during postnatal cerebral cortex vascularization at postnatal day 6, in wild-type (WT) and NG2 knock-out (NG2KO) mice, and in the cortex of adult naïve and EAE-affected WT and NG2KO mice. As observed in WT mice during postnatal development, a higher number of juxtavascular and perivascular OPCs was revealed in adult WT mice during EAE compared to adult naïve WT mice. In EAE-affected mice, OPCs were mostly associated with microvessels that showed altered claudin-5 and occludin tight junction (TJ) staining patterns and barrier leakage. In contrast, EAE-affected NG2KO mice, which did not show any significant increase in vessel-associated OPCs, seemed to retain better preserved TJs and BBB integrity. As expected, absence of NG2, in both OPCs and pericytes, led to a reduced content of vessel basal lamina molecules, laminin, collagen VI, and collagen IV. In addition, analysis of the major ligand/receptor systems known to promote OPC proliferation and migration indicated that vascular endothelial growth factor A (VEGF-A), platelet-derived growth factor-AA (PDGF-AA), and the transforming growth factor-ß (TGF-ß) were the molecules most likely involved in proliferation and recruitment of vascular OPCs during EAE. These results were confirmed by real time-PCR that showed Fgf2, Pdgfa and Tgfb expression on isolated cerebral cortex microvessels and by dual RNAscope-immunohistochemistry/in situ hybridization (IHC/ISH), which detected Vegfa and Vegfr2 transcripts on cerebral cortex sections. Overall, this study suggests that vascular OPCs, in virtue of their developmental arrangement and response to neuroinflammation and growth factors, could be integrated among the classical NVU cell components. Moreover, the synchronized activation of vascular OPCs and pericytes during both BBB development and dysfunction, points to NG2 as a key regulator of vascular interactions.


Assuntos
Antígenos/biossíntese , Barreira Hematoencefálica/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Microvasos/metabolismo , Oligodendroglia/metabolismo , Proteoglicanas/biossíntese , Células-Tronco/metabolismo , Animais , Antígenos/genética , Barreira Hematoencefálica/patologia , Movimento Celular/genética , Proliferação de Células/genética , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Claudina-5/genética , Claudina-5/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/patologia , Camundongos , Camundongos Knockout , Microvasos/patologia , Oligodendroglia/patologia , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteoglicanas/genética , Células-Tronco/patologia , Junções Íntimas/genética , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
PLoS One ; 14(3): e0213539, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30865678

RESUMO

The health and function of tissue rely on its vasculature network to provide reliable blood perfusion. Volumetric imaging approaches, such as multiphoton microscopy, are able to generate detailed 3D images of blood vessels that could contribute to our understanding of the role of vascular structure in normal physiology and in disease mechanisms. The segmentation of vessels, a core image analysis problem, is a bottleneck that has prevented the systematic comparison of 3D vascular architecture across experimental populations. We explored the use of convolutional neural networks to segment 3D vessels within volumetric in vivo images acquired by multiphoton microscopy. We evaluated different network architectures and machine learning techniques in the context of this segmentation problem. We show that our optimized convolutional neural network architecture with a customized loss function, which we call DeepVess, yielded a segmentation accuracy that was better than state-of-the-art methods, while also being orders of magnitude faster than the manual annotation. To explore the effects of aging and Alzheimer's disease on capillaries, we applied DeepVess to 3D images of cortical blood vessels in young and old mouse models of Alzheimer's disease and wild type littermates. We found little difference in the distribution of capillary diameter or tortuosity between these groups, but did note a decrease in the number of longer capillary segments (>75µm) in aged animals as compared to young, in both wild type and Alzheimer's disease mouse models.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Angiografia Cerebral , Córtex Cerebral , Imagem Tridimensional , Microscopia de Fluorescência por Excitação Multifotônica , Animais , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/diagnóstico por imagem , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Transgênicos
14.
J Stroke Cerebrovasc Dis ; 28(6): 1710-1717, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878371

RESUMO

INTRODUCTION: There is continued interest in identifying factors that predict a favorable outcome after endovascular thrombectomy (EVT) for anterior circulation large vessel occlusion (ACLVO). We compared the predictive values of 2 different scoring systems for evaluating venous collateral circulation. METHODS: A retrospective review of patients who underwent EVT for ACLVO at a single institution was performed. Those who underwent preprocedural computed tomography angiography (CTA) were selected. The Cortical Vein Opacification Score (COVES) and Prognostic Evaluation based on Cortical vein score difference In Stroke (PRECISE) score were calculated from each patient's CTA. Our primary outcome of interest was the Modified Rankin Scale (mRS) score at 90 days. RESULTS: A total of 103 patients were included in the study (average age = 68.3 years, median National Institutes of Health Stroke Scale = 15). The mean time to reperfusion was 6.4 hours and Thrombolysis in Cerebral Infarction 2B or 3 reperfusion was achieved in 77.7% of cases. An unfavorable COVES score was significantly associated with an unfavorable (mRS 3-6) outcome (adjusted odds ratio [aOR]: 3.06; 95% confidence interval [CI] 1.15-8.13, P = .025), while an unfavorable PRECISE score was not (aOR: 1.02; 95% CI .37-2.80, P = .966). Based on the Receiver Operating Characteristic analysis, the COVES score had a sensitivity of 68.1%, specificity of 71.4%, and area under the curve (AUC) of .77. The PRECISE score had a sensitivity of 68.9%, specificity of 70.7%, and the AUC of .73. CONCLUSIONS: The COVES score, but not the PRECISE score, is associated with functional outcomes at 90 days after EVT for ACLVO.


Assuntos
Angiografia Cerebral/métodos , Córtex Cerebral/irrigação sanguínea , Veias Cerebrais/diagnóstico por imagem , Circulação Cerebrovascular , Circulação Colateral , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Veias Cerebrais/fisiopatologia , Técnicas de Apoio para a Decisão , Avaliação da Deficiência , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/fisiopatologia , Trombectomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
15.
Biomed Pharmacother ; 113: 108757, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30897537

RESUMO

Previous findings have demonstrated, in a rat model, that chronic cerebral hypoperfusion (CCH) decreases cortical cerebral blood flow (CBF) while Dl-3-n-Butylphthalide (DNB) accelerates the timely recovery of CBF. However, potential biomarkers, therapeutic targets, and underlying mechanisms for these processes are unclear. In this study, a solid-phase antibody microarray for simultaneously detecting multiple proteins was used to search cortex biotargets in CCH compared to a sham control group, and these results were further examined by biological functional analysis. After DNB treatment, western blot and immunostaining were used to verify candidate protein expression. Importantly, we identified seven proteins that may serve as novel biotargets contributing to CCH. The levels of Tie-2, CNTFRα, IL-4, IL-10, ITGAM, MDC, and TROY were uniquely altered in the CCH. The Tie-2 level was significantly decreased and identified in CCH 2 week (W), CCH 4 W and CCH 8 W. In addition, Ang-1 level and Ang-1/Ang-2 ratio were significantly decreased in CCH 2 W and CCH 4 W while Ang-2 level was increased in the CCH, whereas DNB treatment created the inverse effect to some extent. Moreover, the expression of VEGF and CD34 in the earlier stage of CCH and the diameters of bilateral vertebral arteries (VAs), were significantly enlarged by DNB treatment. Together, we found that the Ang-1/Ang-2/Tie-2 signaling axis was altered in the CCH rat cortex, and DNB treatment could timely regulate this angiopoietin/Tie signaling axis to promote neovascularization in early stages.


Assuntos
Benzofuranos/farmacologia , Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Angiopoietina-1/metabolismo , Angiopoietina-2/metabolismo , Animais , Western Blotting , Isquemia Encefálica/tratamento farmacológico , Córtex Cerebral/efeitos dos fármacos , Masculino , Análise Serial de Proteínas/métodos , Ratos , Ratos Sprague-Dawley , Receptor TIE-2/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Alcohol Alcohol ; 54(2): 177-179, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30801636

RESUMO

A 15-year-old girl diagnosed with FASD underwent 100 courses of hyperbasic oxygen therapy (HBOT). Prior to HBOT, single motion emission compute tomographic begin imaging (SPECT) revealed areas of hypo-perfusion bilaterally in the orbitofrontal region, temporal lobes and right dorsolateral-frontal, as well the medial aspect of the left cerebellum. Following two sets of HBOT treatments (60 plus 40), over 6 months, there was improvement in perfusion to the left cerebellum as well as the right frontal lobe. This was paralleled by improvement in immediate cognitive tests and an increase in functional brain volume. A follow-up 18 months after HBOT showed sustained improvement in attention with no need for methylphenidate, as well as in math skills and writing.


Assuntos
Cerebelo/irrigação sanguínea , Córtex Cerebral/irrigação sanguínea , Cognição , Transtornos do Espectro Alcoólico Fetal/terapia , Oxigenação Hiperbárica , Adolescente , Feminino , Humanos , Neuroimagem , Tomografia Computadorizada de Emissão de Fóton Único
17.
J Exp Clin Cancer Res ; 38(1): 9, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621721

RESUMO

BACKGROUND: RNA binding proteins (RBPs) have been reported to interact with RNAs to regulate gene expression. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which involved in the angiogenesis of tumor. The purpose of this study is to elucidate the potential roles and molecular mechanisms of MOV10 and circ-DICER1 in regulating the angiogenesis of glioma-exposed endothelial cells (GECs). METHODS: The expressions of circ-DICER1, miR-103a-3p and miR-382-5p were detected by real-time PCR. The expressions of MOV10, ZIC4, Hsp90 and PI3K/Akt were detected by real-time PCR or western blot. The binding ability of circ-SHKBP1 and miR-544a / miR-379, ZIC4 and miR-544a / miR-379 were analyzed with Dual-Luciferase Reporter System or RIP experiment. The direct effects of ZIC4 on the Hsp90ß promoter were analyzed by the ChIP experiment. The cell viability, migration and tube formation in vitro were detected by CCK-8, Transwell assay and Matrigel tube formation assay. The angiogenesis in vivo was evaluated by Matrigel plug assay. Student's t-test (two tailed) was used for comparisons between two groups. One-way analysis of variance (ANOVA) was used for multi-group comparisons followed by Bonferroni post-hoc analysis. RESULTS: The expressions of RNA binding proteins MOV10, circ-DICER1, ZIC4, and Hsp90ß were up-regulated in GECs, while miR103a-3p/miR-382-5p were down-regulated. MOV10 binding circ-DICER1 regulated the cell viability, migration, and tube formation of GECs. And the effects of both MOV10 and circ-DICER1 silencing were better than the effects of MOV10 or circ-DICER1 alone silencing. In addition, circ-DICER1 acts as a molecular sponge to adsorb miR-103a-3p / miR-382-5p and impair the negative regulation of miR-103a-3p / miR-382-5p on ZIC4 in GECs. Furthermore, ZIC4 up-regulates the expression of its downstream target Hsp90ß, and Hsp90 promotes the cell viability, migration, and tube formation of GECs by activating PI3K/Akt signaling pathway. CONCLUSIONS: MOV10 / circ-DICER1 / miR-103a-3p (miR-382-5p) / ZIC4 pathway plays a vital role in regulating the angiogenesis of glioma. Our findings not only provides novel mechanisms for the angiogenesis of glioma, but also provide potential targets for anti-angiogenesis therapies of glioma.


Assuntos
RNA Helicases DEAD-box/genética , Glioma/genética , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , RNA Helicases/genética , RNA Helicases/metabolismo , Ribonuclease III/genética , Fatores de Transcrição/metabolismo , Animais , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proliferação de Células/fisiologia , Córtex Cerebral/irrigação sanguínea , Glioma/irrigação sanguínea , Glioma/metabolismo , Glioma/patologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Neovascularização Patológica , Transfecção , Regulação para Cima
18.
PLoS One ; 14(1): e0204295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30608925

RESUMO

Microhemorrhages are common in the aging brain and are thought to contribute to cognitive decline and the development of neurodegenerative diseases, such as Alzheimer's disease. Chronic aspirin therapy is widespread in older individuals and decreases the risk of coronary artery occlusions and stroke. There remains a concern that such aspirin usage may prolong bleeding after a vessel rupture in the brain, leading to larger bleeds that cause more damage to the surrounding tissue. Here, we aimed to understand the influence of aspirin usage on the size of cortical microhemorrhages and explored the impact of age. We used femtosecond laser ablation to rupture arterioles in the cortex of both young (2-5 months old) and aged (18-29 months old) mice dosed on aspirin in their drinking water and measured the extent of penetration of both red blood cells and blood plasma into the surrounding tissue. We found no difference in microhemorrhage size for both young and aged mice dosed on aspirin, as compared to controls (hematoma diameter = 104 +/- 39 (97 +/- 38) µm in controls and 109 +/- 25 (101 +/- 28) µm in aspirin-treated young (aged) mice; mean +/- SD). In contrast, young mice treated with intravenous heparin had an increased hematoma diameter of 136 +/- 44 µm. These data suggest that aspirin does not increase the size of microhemorrhages, supporting the safety of aspirin usage.


Assuntos
Aspirina/efeitos adversos , Hemorragia Cerebral/etiologia , Hematoma Subdural Intracraniano/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Índice de Gravidade de Doença , Fatores Etários , Envelhecimento/fisiologia , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/patologia , Arteríolas/cirurgia , Aspirina/administração & dosagem , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/patologia , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Modelos Animais de Doenças , Feminino , Hematoma Subdural Intracraniano/etiologia , Hematoma Subdural Intracraniano/patologia , Hemostasia/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibidores da Agregação de Plaquetas/administração & dosagem
19.
J Stroke Cerebrovasc Dis ; 28(4): e30-e32, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30655044

RESUMO

Cerebral microbleeds (MBs) have been often observed due to the development of imaging devices, and are classified to deep and lobar MBs. Lobar MBs are strongly associated with cerebral amyloid angiopathy. Here, we report 3 cases of lobar MBs that developed after small cortical ischemic stroke. One case underwent carotid artery stenting for severe carotid stenosis, one was diagnosed with artery-to-artery embolism, and the other was embolic stroke of undetermined source. New small cortical infarctions were detected with diffusion-weighted magnetic resonance imaging (MRI). Initial MRI revealed no hemorrhage around the ischemic lesion on T2*-weighted gradient-recalled echo or susceptibility-weighted imaging (SWI) at the onset of stroke. Follow-up SWI after 12-20 months revealed lobar MBs in the previously detected ischemic lesions, and high-intensity lesions remained around the MBs on fluid-attenuated inversion recovery imaging. These cases revealed that cerebral MBs developed through the transformation of small cortical infarctions. All cases showed lobar MBs, and these MBs existed in the previously detected ischemic lesions at a chronic stage. Lobar MBs present around ischemic lesions may predict embolic infarcts.


Assuntos
Estenose das Carótidas/complicações , Córtex Cerebral/irrigação sanguínea , Hemorragia Cerebral/etiologia , Infarto Cerebral/etiologia , Embolia Intracraniana/etiologia , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/cirurgia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/fisiopatologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/fisiopatologia , Circulação Cerebrovascular , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Procedimentos Endovasculares/instrumentação , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/fisiopatologia , Masculino , Stents , Fatores de Tempo
20.
Neuroimage ; 185: 926-933, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29535026

RESUMO

Abnormal cerebral blood flow (CBF) is implicated in several neonatal and infant diseases. However, measurement of CBF in this population remains difficult and has not been used in routine clinical MRI. Arterial spin labeling (ASL) methods suffer from both low SNR and poor quantification when applied to very young children. Furthermore, rapid change in brain physiology in this age range makes it difficult to choose sequence parameters such as labeling pulse flip angle and post labeling delay. Phase-contrast (PC) MRI is another approach to measure flow. It provides fast and reliable global CBF assessment, and has great promises in pediatric applications. In this study, we aimed to apply PC-MRI technique for CBF quantification in neonates and infants up to 18 months of age. We first compared several implementations of time-of-flight (TOF) MR angiogram for the visualization of brain's feeding arteries, which provides anatomical information for the positioning of PC-MRI scans. We then measured flow velocity and CBF of the internal carotid artery (ICA) and vertebral artery (VA) in 21 subjects (age 34-114 gestational weeks, 3 females, 18 males), using six encoding velocities (Venc) in each vessel. In ICA, peak arterial flow velocity was 10.2 cm/s at birth and increased to 56.0 cm/s at 18 months old. These values were 4.5-36.3 cm/s, respectively, for VA. CBF after accounting for brain volume revealed a significant (p < 0.001) age-related increase from 13.1 to 84.7 ml/100  g/min within the first 18 months after birth. Based on the peak flow velocity, we provided age-specific recommendations for Venc selection in PC-MRI when one only has time for one scan. The present study used a multi-Venc scheme to determine flow velocities in major feeding arteries of infant brain and may lay a foundation for accurate measurement of whole-brain CBF in this population.


Assuntos
Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/crescimento & desenvolvimento , Circulação Cerebrovascular , Imagem por Ressonância Magnética/métodos , Neuroimagem/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
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