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1.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445151

RESUMO

Subarachnoid hemorrhage (SAH) is associated with acute and delayed cerebral ischemia. We suggested spasms of pial arterioles as a possible mechanism; however, it remained unclear whether and how pial microvasospasms (MVSs) induce cerebral ischemia. Therefore, we used in vivo deep tissue imaging by two-photon microscopy to investigate MVSs together with the intraparenchymal microcirculation in a clinically relevant murine SAH model. Male C57BL/6 mice received a cranial window. Cerebral vessels and leukocytes were labelled with fluorescent dyes and imaged by in vivo two-photon microscopy before and three hours after SAH induced by filament perforation. After SAH, a large clot formed around the perforation site at the skull base, and blood distributed along the perivascular space of the middle cerebral artery up to the cerebral cortex. Comparing the cerebral microvasculature before and after SAH, we identified three different patterns of constrictions: pearl string, global, and bottleneck. At the same time, the volume of perfused intraparenchymal vessels and blood flow velocity in individual arterioles were significantly reduced by more than 60%. Plugging of capillaries by leukocytes was observed but infrequent. The current study demonstrates that perivascular blood is associated with spasms of pial arterioles and that these spasms result in a significant reduction in cortical perfusion after SAH. Thus, the pial microvasospasm seems to be an important mechanism by which blood in the subarachnoid space triggers cerebral ischemia after SAH. Identifying the mechanisms of pial vasospasm may therefore result in novel therapeutic options for SAH patients.


Assuntos
Encéfalo/irrigação sanguínea , Leucócitos/patologia , Microvasos/patologia , Hemorragia Subaracnóidea/patologia , Vasoespasmo Intracraniano/patologia , Animais , Encéfalo/patologia , Circulação Cerebrovascular , Microscopia Intravital , Masculino , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência por Excitação Multifotônica
2.
Medicine (Baltimore) ; 100(31): e26840, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397854

RESUMO

RATIONALE: We report on a patient whose arcuate fasciculus (AF) and corticobulbar tract (CBT) recovered following an infarct in the middle cerebral artery (MCA) territory, demonstrated on serial diffusion tensor tractography (DTT). PATIENT CONCERNS: The patient showed moderate conduction aphasia on the Western Aphasia Battery with an aphasia quotient of 46.5‰ (spontaneous speech: 35.0‰, auditory comprehension: 36.0‰, and naming: 53.1‰) at 1 month after onset. His aphasia improved with an aphasia quotient of 49‰ (spontaneous speech: 71.0‰, auditory comprehension: 52.0‰, and naming: 59.0‰) at 10 months after onset. DIAGNOSIS: A 44-year-old right-handed male patient presented with aphasia and quadriplegia, which occurred at the onset of an infarct in the left MCA territory. INTERVENTION: Diffusion tensor imaging data were acquired twice (1 month and 10 months after onset). OUTCOMES: On one-month DTT, the discontinuation of the left AF and severe narrowing of the right CBT were observed. However, on ten-month DTT, the left AF was connected to the opposite AF by a new tract that passed through the splenium of corpus callosum, and the right CBT had become thicker. LESSONS: We believe that our results suggest a recovery mechanism of injured AF and CBT in stroke patients.


Assuntos
Afasia , Encéfalo , Área de Broca , Infarto da Artéria Cerebral Média , Área de Wernicke , Adulto , Afasia/diagnóstico , Afasia/etiologia , Afasia/reabilitação , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Humanos , Infarto da Artéria Cerebral Média/diagnóstico , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/reabilitação , Masculino , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Reabilitação Neurológica/métodos , Tratos Piramidais/patologia , Recuperação de Função Fisiológica , Fonoterapia/métodos , Resultado do Tratamento
3.
Nat Neurosci ; 24(9): 1198-1209, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34354283

RESUMO

The brain is supplied by an elaborate vascular network that originates extracranially and reaches deep into the brain. The concept of the neurovascular unit provides a useful framework to investigate how neuronal signals regulate nearby microvessels to support the metabolic needs of the brain, but it does not consider the role of larger cerebral arteries and systemic vasoactive signals. Furthermore, the recently emerged molecular heterogeneity of cerebrovascular cells indicates that there is no prototypical neurovascular unit replicated at all levels of the vascular network. Here, we examine the cellular and molecular diversity of the cerebrovascular tree and the relative contribution of systemic and brain-intrinsic factors to neurovascular function. Evidence supports the concept of a 'neurovascular complex' composed of segmentally diverse functional modules that implement coordinated vascular responses to central and peripheral signals to maintain homeostasis of the brain. This concept has major implications for neurovascular regulation in health and disease and for brain imaging.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Circulação Cerebrovascular/fisiologia , Homeostase/fisiologia , Acoplamento Neurovascular/fisiologia , Animais , Humanos
4.
Int Rev Cell Mol Biol ; 363: 203-269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34392930

RESUMO

An increase in intracellular Ca2+ concentration ([Ca2+]i) regulates a plethora of functions in the cardiovascular (CV) system, including contraction in cardiomyocytes and vascular smooth muscle cells (VSMCs), and angiogenesis in vascular endothelial cells and endothelial colony forming cells. The sarco/endoplasmic reticulum (SR/ER) represents the largest endogenous Ca2+ store, which releases Ca2+ through ryanodine receptors (RyRs) and/or inositol-1,4,5-trisphosphate receptors (InsP3Rs) upon extracellular stimulation. The acidic vesicles of the endolysosomal (EL) compartment represent an additional endogenous Ca2+ store, which is targeted by several second messengers, including nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], and may release intraluminal Ca2+ through multiple Ca2+ permeable channels, including two-pore channels 1 and 2 (TPC1-2) and Transient Receptor Potential Mucolipin 1 (TRPML1). Herein, we discuss the emerging, pathophysiological role of EL Ca2+ signaling in the CV system. We describe the role of cardiac TPCs in ß-adrenoceptor stimulation, arrhythmia, hypertrophy, and ischemia-reperfusion injury. We then illustrate the role of EL Ca2+ signaling in VSMCs, where TPCs promote vasoconstriction and contribute to pulmonary artery hypertension and atherosclerosis, whereas TRPML1 sustains vasodilation and is also involved in atherosclerosis. Subsequently, we describe the mechanisms whereby endothelial TPCs promote vasodilation, contribute to neurovascular coupling in the brain and stimulate angiogenesis and vasculogenesis. Finally, we discuss about the possibility to target TPCs, which are likely to mediate CV cell infection by the Severe Acute Respiratory Disease-Coronavirus-2, with Food and Drug Administration-approved drugs to alleviate the detrimental effects of Coronavirus Disease-19 on the CV system.


Assuntos
COVID-19/complicações , COVID-19/tratamento farmacológico , Sinalização do Cálcio/fisiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Lisossomos/metabolismo , SARS-CoV-2 , ADP-Ribosil Ciclase 1/metabolismo , Animais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , COVID-19/metabolismo , Canais de Cálcio/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Retículo Endoplasmático/metabolismo , Células Endoteliais/metabolismo , Humanos , Modelos Cardiovasculares , Miócitos Cardíacos/metabolismo , NADP/análogos & derivados , NADP/metabolismo , Receptores Adrenérgicos beta/metabolismo , Retículo Sarcoplasmático/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo
5.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299328

RESUMO

The blood-brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer's disease and Parkinson's disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area.


Assuntos
Barreira Hematoencefálica/metabolismo , Encéfalo/citologia , Encéfalo/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Doenças Neurodegenerativas/metabolismo , Animais , Barreira Hematoencefálica/citologia , Barreira Hematoencefálica/patologia , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Modelos Biológicos , Doenças Neurodegenerativas/patologia
7.
Commun Biol ; 4(1): 855, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244604

RESUMO

The spatial-temporal sequence of cerebral blood flow (CBF), cerebral blood volume (CBV) and blood velocity changes triggered by neuronal activation is critical for understanding functional brain imaging. This sequence follows a stereotypic pattern of changes across different zones of the vasculature in the olfactory bulb, the first relay of olfaction. However, in the cerebral cortex, where most human brain mapping studies are performed, the timing of activity evoked vascular events remains controversial. Here we utilized a single whisker stimulation model to map out functional hyperemia along vascular arbours from layer II/III to the surface of primary somatosensory cortex, in anesthetized and awake Thy1-GCaMP6 mice. We demonstrate that sensory stimulation triggers an increase in blood velocity within the mid-capillary bed and a dilation of upstream large capillaries, and the penetrating and pial arterioles. We report that under physiological stimulation, response onset times are highly variable across compartments of different vascular arbours. Furthermore, generating transfer functions (TFs) between neuronal Ca2+ and vascular dynamics across different brain states demonstrates that anesthesia decelerates neurovascular coupling (NVC). This spatial-temporal pattern of vascular events demonstrates functional diversity not only between different brain regions but also at the level of different vascular arbours within supragranular layers of the cerebral cortex.


Assuntos
Encéfalo/fisiologia , Córtex Cerebral/fisiologia , Circulação Cerebrovascular/fisiologia , Acoplamento Neurovascular/fisiologia , Córtex Somatossensorial/fisiologia , Animais , Encéfalo/irrigação sanguínea , Mapeamento Encefálico/métodos , Capilares/fisiologia , Córtex Cerebral/irrigação sanguínea , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Neuroimagem/métodos , Neurônios/fisiologia , Bulbo Olfatório/irrigação sanguínea , Bulbo Olfatório/fisiologia , Córtex Somatossensorial/irrigação sanguínea , Vibrissas/fisiologia , Vigília/fisiologia
8.
J Stroke Cerebrovasc Dis ; 30(9): 105952, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34214963

RESUMO

OBJECTIVE: Cerebral Blood Flow (CBF) change after Subarachnoid Hemorrhage (SAH) is strongly associated with brain injuries such as early brain injury and delayed cerebral ischemia. We evaluated the correlation between CBF using Laser Speckle Flow Imaging (LSFI) after SAH and neurological findings in the sub-acute phase. METHOD: An SAH was induced by endovascular perforation in male mice. CBF was quantitatively measured by using LSFI at six time points, immediately to 14 days after SAH induction. Behavior tests and survival rate were evaluated. The mice were divided into recovery and hypo-perfusion groups according to their CBF at 1 day after the procedure. RESULT: Forty mice were included in this study. Five mice (20%) were included in the hypo-perfusion group, and the remaining 20 (80%) mice were classified as the recovery group. The decrease of CBF in the recovery group was observed until 1 day after the procedure. However, the decrease of CBF in the hypo-perfusion group was prolonged until 7 days after the procedure. Neurological findings and survival rates in the hypo-perfusion group were significantly worse than those in the recovery group. The low alternation cases (≤ 50%) in the Y-maze test in the recovery group (n = 5) had significantly lower CBF at 1 day after the procedure. CONCLUSION: Low blood flow at 1 day after SAH was associated with worse survival rate, neurological findings, and memory disturbance. Early improvement in CBF may be associated with an improved prognosis after SAH.


Assuntos
Comportamento Animal , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular , Transtornos da Memória/fisiopatologia , Memória , Hemorragia Subaracnóidea/fisiopatologia , Animais , Velocidade do Fluxo Sanguíneo , Cognição , Modelos Animais de Doenças , Imagem de Contraste de Manchas a Laser , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Camundongos , Imagem de Perfusão , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/psicologia , Fatores de Tempo
9.
Medicine (Baltimore) ; 100(25): e26486, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160462

RESUMO

BACKGROUND: : Discovery of evidence of acute brain ischemia or hypoxia and its differentiation from agonal hypoxia represents a task of interest but extremely difficult in forensic neuropathology. Generally, more than 50% of forensic autopsies indicate evidence of brain induced functional arrest of the organ system, which can be the result of a hypoxic/ischemic brain event. Even if the brain is the target organ of hypoxic/ischemic damage, at present, there are no specific neuropathological (macroscopic and histological) findings of hypoxic damage (such as in drowning, hanging, intoxication with carbon monoxide) or acute ischemia. In fact, the first histological signs appear after at least 4 to 6 hours. Numerous authors have pointed out how an immunohistochemical analysis could help diagnose acute cerebral hypoxia/ischemia.Data sources: This review was based on articles published in PubMed and Scopus databases in the past 25 years, with the following keywords "immunohistochemical markers," "acute cerebral ischemia," "ischemic or hypoxic brain damage," and "acute cerebral hypoxia". OBJECTIVES: : Original articles and reviews on this topic were selected. The purpose of this review is to analyze and summarize the markers studied so far and to consider the limits of immunohistochemistry that exist to date in this specific field of forensic pathology. RESULTS: : We identified 13 markers that had been examined (in previous studies) for this purpose. In our opinion, it is difficult to identify reliable and confirmed biomarkers from multiple studies in order to support a postmortem diagnosis of acute cerebral hypoxia/ischemia. Microtubule-associated protein 2 (MAP2) is the most researched marker in the literature and the results obtained have proven to be quite useful. CONCLUSION: Immunohistochemistry has provided interesting and promising results, but further studies are needed in order to confirm and apply them in standard forensic practice.


Assuntos
Autopsia/métodos , Encéfalo/patologia , Hipóxia-Isquemia Encefálica/diagnóstico , Imuno-Histoquímica , Doença Aguda , Animais , Biomarcadores/análise , Encéfalo/irrigação sanguínea , Modelos Animais de Doenças , Humanos , Hipóxia-Isquemia Encefálica/mortalidade , Hipóxia-Isquemia Encefálica/patologia , Proteínas Associadas aos Microtúbulos/análise , Reprodutibilidade dos Testes , Fatores de Tempo
10.
Aging (Albany NY) ; 13(11): 15353-15365, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34086605

RESUMO

Blood brain barrier (BBB) dysfunction developed with aging is related to brain microvascular endothelial cells (BMECs) injury and losses of tight junctions (TJs). In the present study, we found that Alisol A 24-acetate (AA), a natural compound frequently used as treatment against vascular diseases was essential for BMECs injury and TJs degradation. Our experimental results showed that AA enhanced cell viability and increased zonula occludens-1 (ZO-1), claudin-5, and occludin expression in the oxygen-glucose deprivation (OGD)-induced BMECs. The exploration of the underlying mechanism revealed that AA restrained miR-92a-3p, a noncoding RNA involved in endothelial cells senescence and TJs impairment. To test the role of the miR-92a-3p in BMECs, the cells were transfected with miR-92a-3p mimics and inhibitor. The results showed that miR-92a-3p mimics inhibited cell viability and elevated lactate dehydrogenase (LDH) levels as well as suppressed ZO-1, claudin-5 and occludin expression, while the miR-92a-3p inhibitor reversed the above results. These findings were similar to the therapeutic effects of AA in the OGD-induced BMECs. Bioinformatics analysis and dual-luciferase assay confirmed ZO-1 and occludin were the target genes of miR-92a-3p mediated AA protective roles. In summary, the data demonstrated that AA protected against BMECs damage and TJs loss through the inhibition of miR-92a-3p expression. This provided evidence for AA application in aging-associated BBB protection.


Assuntos
Encéfalo/irrigação sanguínea , Colestenonas/farmacologia , Citoproteção/efeitos dos fármacos , Células Endoteliais/patologia , MicroRNAs/metabolismo , Microvasos/patologia , Junções Íntimas/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colestenonas/química , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/deficiência , L-Lactato Desidrogenase/metabolismo , Camundongos , MicroRNAs/genética , Oxigênio , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos
11.
Br J Radiol ; 94(1125): 20201450, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34106749

RESUMO

OBJECTIVE: Blood flow is the rate of blood movement and relevant to numerous processes, though understudied in gliomas. The aim of this review was to pool blood flow metrics obtained from MRI modalities in adult supratentorial gliomas. METHODS: MEDLINE, EMBASE and the Cochrane database were queried 01/01/2000-31/12/2019. Studies measuring blood flow in adult Grade II-IV supratentorial gliomas using dynamic susceptibility contrast (DSC) MRI, dynamic contrast enhanced MRI (DCE-MRI) or arterial spin labelling (ASL) were included. Absolute and relative cerebral blood flow (CBF), peritumoral blood flow and tumoral blood flow (TBF) were reported. RESULTS: 34 studies were included with 1415 patients and 1460 scans. The mean age was 52.4 ± 7.3 years. Most patients had glioblastoma (n = 880, 64.6%). The most common imaging modality was ASL (n = 765, 52.4%) followed by DSC (n = 538, 36.8%). Most studies were performed pre-operatively (n = 1268, 86.8%). With increasing glioma grade (II vs IV), TBF increased (70.8 vs 145.5 ml/100 g/min, p < 0.001) and CBF decreased (85.3 vs 49.6 ml/100 g/min, p < 0.001). In Grade IV gliomas, following treatment, CBF increased in ipsilateral (24.9 ± 1.2 vs 26.1 ± 0.0 ml/100 g/min, p < 0.001) and contralateral white matter (25.6 ± 0.2 vs 26.0± 0.0 ml/100 g/min, p < 0.001). CONCLUSION: Our findings demonstrate that increased mass effect from high-grade gliomas impairs blood flow within the surrounding brain that can improve with surgery. ADVANCES IN KNOWLEDGE: This systematic review demonstrates how mass effect from brain tumours impairs blood flow in the surrounding brain parenchyma that can improve with treatment.


Assuntos
Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/diagnóstico por imagem , Circulação Cerebrovascular , Glioma/irrigação sanguínea , Glioma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Gradação de Tumores
12.
Medicine (Baltimore) ; 100(26): e26498, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190179

RESUMO

ABSTRACT: There was a controversy for the electrocardiogram (ECG) changes and their relationship with disease severity in old patients with acute cerebral ischemic stroke (CIS). This study was aim to provide referential data for this topic.Totally 200 old patients with acute CIS in our hospital from January 2017 to December 2019 were included into this study. According to the ST-T segment changes in ECG, these patients were divided into 3 groups: persistent ischemic group (n = 38), transient ischemic group (n = 106) and non-ischemic group (n = 56). The characteristics and incidence of abnormal ECG and their relationship with disease severity, infarct size and prognosis were respectively analyzed under the severe, moderate and mild type of disease.The ECG changes of patients were mainly characterized by myocardial ischemic ST-T segment changes with a abnormal ECG incidence of 72.00%, the arrhythmia with a abnormal ECG incidence of 9.50%, which were the second most common in clinical features. There were statistically significant differences of myocardial ischemic ST-T segment changes among different disease severity, infarct size and prognosis of acute CIS patients (P < .05). The ischemic ST-T segment changes of ECG reflected that the disease severity, and more ECG abnormalities indicated more severe pathological conditions in CIS patients.The characteristics of ischemic ST-T segment changes have important reference value in the evaluation of severity and prognosis of acute CIS in old patients.


Assuntos
Encéfalo , Eletrocardiografia , AVC Isquêmico , Isquemia Miocárdica , Acidente Vascular Cerebral , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/etiologia , China/epidemiologia , Correlação de Dados , Eletrocardiografia/métodos , Eletrocardiografia/estatística & dados numéricos , Feminino , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , AVC Isquêmico/fisiopatologia , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/etiologia , Masculino , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/fisiopatologia , Prognóstico , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia
13.
Nutrients ; 13(6)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072860

RESUMO

Of the 1575 participants of the CCSVI-Tracking Survey, 475 patients recorded their quality of life and EDSS outcomes for at least 2 months. Self-reported use of complementary and conventional therapies included diet, use of drug therapy, symptoms, quality of life, and mobility. Analysis included comparing outcomes related to different diets within and between groups. Adherence to the MS diet was not associated with a greater quality of life, less disability, a lower Symptom Score, or faster walking speed compared to other diets. Alternately, the participants from the Mediterranean diet region as a whole (µ = 32.65 (SD = 11.37, SEM = 2.37, p = 0.05) had a significantly greater QoL (µ = 60, p = 0.05) and a lower MS symptom score, µ = 32.65 (11.37), p = 0.0029. A decline of symptoms was observed in all diet groups over 3 months with the most dramatic decline observed in participants from the Eastern Mediterranean diet region. The main effect for the within-subjects factor was significant, F(3, 1056) = 55.95, p < 0.001, indicating that there were significant differences between the groups.


Assuntos
Dieta/métodos , Esclerose Múltipla/complicações , Esclerose Múltipla/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Autorrelato , Insuficiência Venosa/complicações , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Doença Crônica , Dieta Mediterrânea , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Qualidade de Vida , Medula Espinal/irrigação sanguínea , Medula Espinal/fisiopatologia , Insuficiência Venosa/fisiopatologia , Insuficiência Venosa/terapia , Caminhada
14.
J Stroke Cerebrovasc Dis ; 30(8): 105864, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34062312

RESUMO

OBJECTIVE: Vascular dementia (VaD) is the second most common cause of dementia and a major health concern worldwide. A comprehensive review on VaD is warranted for better understanding and guidance for the practitioner. We provide an updated overview of the epidemiology, pathophysiological mechanisms, neuroimaging patterns as well as current diagnostic and therapeutic approaches. MATERIALS AND METHODS: A narrative review of current literature in VaD was performed based on publications from the database of PubMed, Scopus and Google Scholar up to January, 2021. RESULTS: VaD can be the result of ischemic or hemorrhagic tissue injury in a particular region of the brain which translates into clinically significant cognitive impairment. For example, a cerebral infarct in the speech area of the dominant hemisphere would translate into clinically significant impairment as would involvement of projection pathways such as the arcuate fasciculus. Specific involvement of the angular gyrus of the dominant hemisphere, with resultant Gerstman's syndrome, could have a pronounced effect on functional ability despite being termed a "minor stroke". Small vessel cerebrovascular disease can have a cumulate effect on cognitive function over time. It is unfortunately well recognized that "good" functional recovery in acute ischemic or haemorrhagic stroke, including subarachnoid haemorrhage, does not necessarily translate into good cognitive recovery. The victim may often be left unable to have gainful employment, drive a car safely or handle their affairs independently. CONCLUSIONS: This review should serve as a compendium of updated information on VaD and provide guidance in terms of newer diagnostic and potential therapeutic approaches.


Assuntos
Encéfalo/irrigação sanguínea , Doenças de Pequenos Vasos Cerebrais/complicações , Circulação Cerebrovascular , Cognição , Demência Vascular/etiologia , AVC Hemorrágico/complicações , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Doenças de Pequenos Vasos Cerebrais/terapia , Demência Vascular/fisiopatologia , Demência Vascular/psicologia , Demência Vascular/terapia , Progressão da Doença , AVC Hemorrágico/fisiopatologia , AVC Hemorrágico/terapia , Humanos , Prognóstico , Recuperação de Função Fisiológica , Fatores de Risco
15.
J Stroke Cerebrovasc Dis ; 30(8): 105885, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34107416

RESUMO

BACKGROUND: Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used to quantify cerebral blood perfusion by labeling blood water as it flows throughout the brain. Hypoperfusion volume ratio (HVR) can be calculated using proportional hypoperfusion volume on ASL-based cerebral blood flow (CBF). This study aimed to explore the relation between HVR and early neurological deterioration (END) in AIS patients. SUBJECTS AND METHODS: Patients with AIS were recruited consecutively, and ASL and regular MRI scans were performed. HVR was calculated from 1.5 and 2.5s post labeling delay (PLD) ASL-CBF maps. END was defined as ≥2 points increment of NIHSS within 72 hours of stroke onset. Univariate and multivariate analysis were used to evaluate the relation between HVR and END. Receiver operating characteristic (ROC) curves were used to determine the ability of HVR in predicting END. RESULTS: Of the 52 enrolled patients, 18 (34.5%) were determined with END. In patients with END, the median hypoperfusion volume was 20 mL [Inter Quartile Range)IQR, 6-72.5 mL] at 1.5s PLD, and 11.2 mL (IQR, 5.3-26 mL) at 2.5s PLD; Sixteen (88.9%) patients had HVR ≥50%, and 13 (72.2%) patients hypoperfusion volume at 2.5s PLD ASL were greater than diffusion-weighted imaging (DWI) infarct volume. In patients without END, median hypoperfusion volume was 7 mL (IQR, 4-30 mL) at 1.5s PLD, and 4 mL (IQR, 1.5-8.5 mL) at 2.5s; Eleven (32.4%) patients had HVR ≥50%, and 10 (29.4%) patients hypoperfusion volume at 2.5s PLD ASL were greater than DWI infarct volume. The proportion of HVR ≥50% and hypoperfusion volume >DWI infarct volume were more frequent in patients with END than patients without (all P<0.001). After adjusted for age, admission NIHSS, proportion of hypoperfusion volume > DWI infarct and arterial transit artifact (ATA) by logistic regression analysis, HVR ≥50% (OR=13.1, P=0.003) was an independent risk factor for END. ROC analysis demonstrated that the HVR could predict END with an area under the curve of 0.794 (P=0.001). CONCLUSIONS: HVR obtained from the 1.5 and 2.5s PLD ASL may be a useful predictor of END in AIS. The value of HVR may be a marker for hemodynamic impairments.


Assuntos
Encéfalo/irrigação sanguínea , Circulação Cerebrovascular , AVC Isquêmico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Imagem de Perfusão , Marcadores de Spin , Idoso , Avaliação da Deficiência , Progressão da Doença , Feminino , Estado Funcional , Humanos , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Medição de Risco , Fatores de Risco
16.
Eur J Vasc Endovasc Surg ; 61(6): 888-899, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33966986

RESUMO

OBJECTIVE: The aim was to evaluate the relationship between asymptomatic carotid stenosis (ACS) of any severity and cognitive impairment and to determine whether there is evidence supporting an aetiological role for ACS in the pathophysiology of cognitive impairment. DATA SOURCES: PubMed/Medline, Embase, Scopus, and the Cochrane library. REVIEW METHODS: This was a systematic review (35 cross sectional or longitudinal studies) RESULTS: Study heterogeneity confounded data interpretation, largely because of no standardisation regarding cognitive testing. In the 30 cross sectional and six longitudinal studies (one included both), 33/35 (94%) reported an association between any degree of ACS and one or more tests of impaired cognitive function (20 reported one to three tests with poorer cognition; 11 reported four to six tests with poorer cognition, while three studies reported seven or more tests with poorer cognition). There was no evidence that ACS caused cognitive impairment via silent cortical infarction, or via involvement in the pathophysiology of lacunar infarction or white matter hyperintensities. However, nine of 10 studies evaluating cerebral vascular reserve (CVR) reported that ACS patients with impaired CVR were significantly more likely to have cognitive impairment and that impaired CVR was associated with worsening cognition over time. Patients with severe ACS but normal CVR had cognitive scores similar to controls. CONCLUSION: Notwithstanding significant heterogeneity within the constituent studies, which compromised overall interpretation, 94% of studies reported an association between ACS and one or more tests of cognitive impairment. However, "significant association" does not automatically imply an aetiological relationship. At present, there is no clear evidence that ACS causes cognitive impairment via silent cortical infarction (but very few studies have addressed this question) and no evidence of ACS involvement in the pathophysiology of white matter hyperintensities or lacunar infarction. There is, however, better evidence that patients with severe ACS and impaired CVR are more likely to have cognitive impairment and to suffer further cognitive decline with time.


Assuntos
Encéfalo/irrigação sanguínea , Estenose das Carótidas , Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Doenças Assintomáticas , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/psicologia , Estudos Transversais , Humanos , Estudos Longitudinais
17.
Methods Mol Biol ; 2311: 185-193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34033087

RESUMO

Studies of blood-brain barrier (BBB) require developing of a novel and convenient in vitro endothelial cell model. We isolated primary human and rodent brain microvascular endothelial cells and developed methods for culturing, characterization, and high-efficiency transfection of endothelial cells. Here, we describe the improved methods to obtain in vitro human and rodent BBB models to study expression of endogenous and exogenous genes of interest.


Assuntos
Barreira Hematoencefálica/fisiologia , Encéfalo/irrigação sanguínea , Separação Celular , Células Endoteliais/fisiologia , Microvasos/citologia , Transfecção , Animais , Barreira Hematoencefálica/metabolismo , Técnicas de Cultura de Células , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Células Endoteliais/metabolismo , Feto , Idade Gestacional , Humanos , Camundongos , Ratos
18.
Obstet Gynecol Clin North Am ; 48(2): 311-323, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33972068

RESUMO

Fetal growth restriction (FGR) describes a fetus' inability to attain adequate weight gain based on genetic potential and gestational age and is the second most common cause of perinatal morbidity and mortality after prematurity. Infants who have suffered fetal growth restriction are at the greatest risks for short- and long-term complications. This article specifically details the neurologic and cardiometabolic sequalae associated with fetal growth restriction, as well as the purported mechanisms that underlie their pathogenesis. We end with a brief discussion about further work that is needed to gain a more complete understanding of fetal growth restriction.


Assuntos
Doenças Cardiovasculares/epidemiologia , Retardo do Crescimento Fetal/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional , Síndrome Metabólica/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Doenças Cardiovasculares/complicações , Epigenômica/métodos , Feminino , Retardo do Crescimento Fetal/genética , Peso Fetal , Feto , Expressão Gênica , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Masculino , Síndrome Metabólica/complicações , Doenças do Sistema Nervoso/complicações , Gravidez , Fatores de Risco
19.
J Alzheimers Dis ; 82(2): 561-573, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34057087

RESUMO

BACKGROUND: Cerebrovascular disease (CeVD) is an underlying cause of cognitive impairment and dementia. Hypertension is a known risk factor of CeVD, but the effects of mean of visit-to-visit blood pressure (BP) on incident CeVD and functional-cognitive decline remains unclear. OBJECTIVE: To determine the association between mean of visit-to-visit BP with the incidence and progression of CeVD [white matter hyperintensities (WMH), infarcts (cortical infarcts and lacunes), cerebral microbleeds (CMBs), intracranial stenosis, and hippocampal volume] as well as functional-cognitive decline over 2 years of follow-up. METHODS: 373 patients from a memory-clinic underwent BP measurements at baseline, year 1, and year 2. The mean of visit-to-visit systolic BP, diastolic BP, pulse pressure, and mean arterial pressure were calculated. Baseline and year 2 MRI scans were graded for WMH, infarcts, CMBs, intracranial stenosis, and hippocampal volume. Functional-cognitive decline was assessed using locally validated protocol. Logistic and linear regression models with odds ratios, mean difference, and 95%confidence interval were constructed to analyze associations of visit-to-visit BP on CeVD incidence and progression as well as functional-cognitive decline. RESULTS: Higher mean of visit-to-visit diastolic BP was associated with WMH progression. Higher tertiles of diastolic BP was associated with WMH progression and incident CMBs. There was no association between mean of visit-to-visit BP measures with incident cerebral infarcts, intracranial stenosis, change in hippocampal volume, and functional-cognitive decline. CONCLUSION: These findings suggest the possibility of hypertension-related vascular brain damage. Careful monitoring and management of BP in elderly patients is essential to reduce the incidence and progression of CeVD.


Assuntos
Encéfalo , Transtornos Cerebrovasculares , Disfunção Cognitiva , Hipertensão , Idoso , Assistência Ambulatorial/estatística & dados numéricos , Monitorização Ambulatorial da Pressão Arterial/métodos , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/fisiopatologia , Progressão da Doença , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/psicologia , Imageamento por Ressonância Magnética/métodos , Masculino , Testes Neuropsicológicos , Medição de Risco , Fatores de Risco , Singapura/epidemiologia
20.
Biochem Biophys Res Commun ; 559: 222-229, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33962209

RESUMO

As one of the natural triterpenoids isolated from Anemone Raddeana Regel, Raddeanin A (RA) has been confirmed to possess therapeutic effects against multiple tumorigeneses, especially for the onset of glioblastoma and growth in human brains. However, the mechanism by which this happens remains poorly understood in terms of the vascular endothelium trafficking routine of RA through the brain-blood barrier (BBB). To seek such answers, human brain microenvironment endothelial cells (HBMECs) were used to stimulate the microenvironment in vitro, and to explore the intracellular accumulation of RA. The results of this experiment illustrated that RA has a relative moderate transport affinity for such cells. The kinetic parameter Km was 37.01 ± 2.116 µM and Vmax was 9.412 ± 0.1375 nM/min/mg of protein. Interestingly, protein downregulation of P-glycoprotein (P-gp, ABCB1/MDR1) significantly activated RA transmembrane activity, which proves that P-gp is responsible for RA cellular trafficking. In addition, the selective non-specific inhibitor, LY335979 increased either RA or the classical substrate of P-gp, digoxin, intracellular accumulation by restricting the transporter's function but without jeopardizing cytomembrane proteins. Moreover, a decrease in the expression or activity of P-gp triggered RA drug resistance to HBMECs. In summary, our data showed that both the expression and function of P-gp are all necessary for RA transmembrane trafficking through cerebrovascular endothelial cells. This study provides significant evidence for the presence of a connection between RA transport and P-gp variation during drug BBB penetration. It is also suggesting some vital guidance on the RA pharmacodynamic effect in human brains.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Encéfalo/irrigação sanguínea , Células Endoteliais/metabolismo , Saponinas/metabolismo , Transporte Biológico , Resistência a Medicamentos , Humanos , Espaço Intracelular/metabolismo , Microvasos/metabolismo
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