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1.
Saudi Med J ; 42(4): 391-398, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33795494

RESUMEN

OBJECTIVES: To determine the demographic and clinical characteristics, underlying comorbidities, and outcomes of children with coronavirus disease 2019 (COVID-19) infection. METHODS: In this retrospective study, we reported 62 pediatric patients (age <14 years) with confirmed COVID-19 between March 2 and July 1, 2020, at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. RESULTS: Comorbid conditions, including cardiac, neurological, respiratory, and malignant disorders, were reported in 9 patients (14.5%). The most prominent presenting complaints were fever (80.6%) and cough (48.4%). Most of our patients (80.6%) had mild disease, 11.3% had moderate disease, and 8.1% exhibited severe and critical illness. Twenty-one patients (33.9%) were hospitalized, with 4 patients (6.5%) admitted to the pediatric intensive care unit, and 3 (4.8%) patients died. CONCLUSION: All pediatric age groups are susceptible to COVID-19, with no gender difference. COVID-19 infection may result in critical illness and even mortality in subsets of pediatric patients.


Asunto(s)
/fisiopatología , Dolor Abdominal/fisiopatología , Adolescente , Asma/epidemiología , Atrofia , Encéfalo/patología , Bronquiolitis Obliterante/epidemiología , /epidemiología , Niño , Preescolar , Comorbilidad , Tos/fisiopatología , Diarrea/fisiopatología , Disnea/fisiopatología , Femenino , Fiebre/fisiopatología , Cardiopatías Congénitas/epidemiología , Mortalidad Hospitalaria , Hospitalización , Humanos , Hidrocefalia/epidemiología , Lactante , Unidades de Cuidado Intensivo Pediátrico , Masculino , Faringitis/fisiopatología , Respiración Artificial , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , Arabia Saudita/epidemiología , Índice de Severidad de la Enfermedad , Vómitos/fisiopatología
2.
Artículo en Ruso | MEDLINE | ID: mdl-33834716

RESUMEN

OBJECTIVE: To develop and implement the tactics of the differentiated complex (medication in combination with surgery) treatment of the form of Parkinson's disease (PD) associated with dyskinesias, according to the severity of atrophic changes in the brain. MATERIAL AND METHODS: The study included 40 patients with PD associated with dyskinesias and motor fluctuations. Patients of the main group received medication and surgical treatment, patients of the comparison group received only medication. The patient's health was assessed every 3 months during 1.5 years. Three atrophy indices were proposed to describe atrophic changes in the brain. RESULTS: We have determined the values of the indices when the complex treatment was optimal for patients. CONCLUSION: The results of the study are supposed to be used in the practice of neurologists and neurosurgeons.


Asunto(s)
Discinesias , Enfermedad de Parkinson , Antiparkinsonianos/uso terapéutico , Atrofia/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología
3.
J Comput Assist Tomogr ; 45(2): 285-293, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33661150

RESUMEN

PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial arteriopathy characterized by recurrent lacunar stroke, migraine, and depression. The mechanism of cognitive dysfunction in CADASIL is still uncertain. The aim of this study was to use tract-based spatial statistics (TBSS) to map voxelwise the spatial distribution of brain microstructural change revealed by DTI-derived indices in patients with CADASIL to further study the underlying neuropsychopathological mechanism of CADASIL. METHOD: Twelve patients with CADASIL and 11 age-, sex-matched healthy controls underwent magnetic resonance imaging at 3 T. Then we evaluated DTI-derived indices (fractional anisotropy [FA], mode of anisotropy [MO], mean diffusivity [MD], axial diffusivity [AD] and radial diffusivity [RD]) of brain white matter (WM) between CADASIL patients and healthy subjects through TBSS. RESULTS: Compared with healthy controls, patients with CADASIL showed extensive decreased FA, MO and increased RD, AD, and MD throughout the entire brain (mainly the WM of the temporal poles, inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corpus callosum, uncinate fasciculus, internal capsule, external capsule, corona radiata, thalamic radiation, and cingulum). Furthermore, these WM microstructural alterations were significantly correlated with cognitive scores and Scheltens scores. Decreased FA values and MO values were positively correlated with Montreal Cognitive Assessment scores in CADASIL patients. Increased AD, RD, and MD values were significantly negatively correlated with Montreal Cognitive Assessment scores. CONCLUSIONS: Widespread WM abnormalities were clearly shown in CADASIL by using TBSS. Severity of microstructural changes correlates significantly with extension of T2 hyperintensity. Moreover, WM microstructural damage and cognitive impairment were significantly correlated. This study indicated that WM tract damage plays an important role in cognitive impairment in CADASIL.


Asunto(s)
Encéfalo/diagnóstico por imagen , CADASIL/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Imagen de Difusión Tensora , Adulto , Encéfalo/patología , CADASIL/complicaciones , CADASIL/patología , Estudios de Casos y Controles , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad
4.
Life Sci ; 273: 119303, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33667518

RESUMEN

AIM: The current study aims to investigate the impact of paradoxical (REM) sleep deprivation and/or epileptic seizures on rat's cortical brain tissues. MAIN METHODS: Animals were divided into four groups; control, epileptic, REM sleep deprived and epileptic subjected to REM sleep deprivation. Electrocorticogram (ECoG) signals were recorded and quantitatively analyzed for each group. Concentrations of amino acid neurotransmitters; proinflammatory cytokines; and oxidative stress parameters; and acetylcholinesterase activity were determined in the cortex of the animals in different groups. KEY FINDINGS: Results showed significant variations in the spectral distribution of ECoG waves in the epilepsy model, 24- and 48-hours of REM sleep deprivation and their combined effects indicating a state of cortical hyperexcitability. Significant increases in NO and taurine and significant decrement in glutamine, GABA and glycine were determined. In REM sleep deprived rats significant elevation in glutamate, aspartate, glycine and taurine and a significant lowering in GABA were obtained. This was accompanied by significant reduction in AchE and IL-ß. In the cortical tissue of epileptic rats deprived from REM sleep significant increases in lipid peroxidation, TNF-α, IL-1ß, IL-6 and aspartate and a significant reduction in AchE were observed. SIGNIFICANCE: The present data indicate that REM sleep deprivation induces an increase in lipid peroxidation and storming in proinflammatory cytokines in the cortex of rat model of epilepsy during SRS. These changes are associated with a decreased seizure threshold as inferred from the increase in alpha and Beta waves and a decrease in Delta waves of ECoG.


Asunto(s)
Encéfalo/patología , Neurotransmisores/toxicidad , Estrés Oxidativo/efectos de los fármacos , Convulsiones/complicaciones , Privación de Sueño/complicaciones , Sueño REM/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Electrofisiología , Peroxidación de Lípido , Masculino , Ratas , Ratas Wistar
5.
Eur J Endocrinol ; 184(4): 565-574, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33730688

RESUMEN

Design: Cushing's disease (CD) is a rare clinical syndrome characterized by chronic exposure to hypercortisolism due to an adrenocorticotropic hormone-secreting pituitary adenoma. The adverse effects of chronic exposure to hypercortisolism on the human brain remain unclear. The purpose of this study was to assess the prevalence of cerebral microbleeds (CMBs) in CD patients and their associations with clinical characteristics. Methods: In this study, 48 active CD patients, 39 remitted CD patients, and 52 healthy control (HC) subjects underwent MRI. CD patients also underwent neuropsychological testing and clinical examinations. The number, locations, and volumes of CMBs were assessed on quantitative susceptibility mapping (QSM) images and with the Microbleed Anatomical Rating Scale. The correlation between CMBs and clinical characteristics was explored. Results: The prevalence of CMBs among active and remitted CD patients was higher than that among HCs (16.3%, 20.5%, and 3.3%, respectively). Moreover, the age of CD patients with CMBs were much younger than HCs with CMBs. Furthermore, the increased number of CMBs in active CD patients was associated with increased cerebrospinal fluid (CSF) volumes in remitted CD patients. Conclusions: Chronic exposure to hypercortisolism may be relevant to CMBs and significantly correlated with altered brain volumes in CD.


Asunto(s)
Encéfalo/diagnóstico por imagen , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiología , Imagen por Resonancia Magnética/métodos , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/complicaciones , Adulto , Anciano , Encéfalo/patología , Mapeo Encefálico/métodos , Estudios de Casos y Controles , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/patología , Estudios Transversales , Síndrome de Cushing/complicaciones , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/epidemiología , Síndrome de Cushing/patología , Susceptibilidad a Enfermedades/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/epidemiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/patología , Prevalencia
6.
Nat Biomed Eng ; 5(3): 219-228, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33723412

RESUMEN

Changes in cerebral blood flow are associated with stroke, aneurysms, vascular cognitive impairment, neurodegenerative diseases and other pathologies. Brain angiograms, typically performed via computed tomography or magnetic resonance imaging, are limited to millimetre-scale resolution and are insensitive to blood-flow dynamics. Here we show that ultrafast ultrasound localization microscopy of intravenously injected microbubbles enables transcranial imaging of deep vasculature in the adult human brain at microscopic resolution and the quantification of haemodynamic parameters. Adaptive speckle tracking to correct for micrometric brain-motion artefacts and ultrasonic-wave aberrations induced during transcranial propagation allowed us to map the vascular network of tangled arteries to functionally characterize blood-flow dynamics at a resolution of up to 25 µm and to detect blood vortices in a small deep-seated aneurysm in a patient. Ultrafast ultrasound localization microscopy may facilitate the understanding of brain haemodynamics and of how vascular abnormalities in the brain are related to neurological pathologies.


Asunto(s)
Arterias/patología , Encéfalo/patología , Circulación Cerebrovascular/fisiología , Microscopía/métodos , Ultrasonografía/métodos , Humanos , Microburbujas , Movimiento (Física)
7.
Anticancer Res ; 41(3): 1445-1449, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33788736

RESUMEN

BACKGROUND: Limited brain metastasis is treated definitively with stereotactic radiosurgery when surgical resection is not indicated. Although this has historically been performed in a single fraction, multi-fraction approaches such as fraction radiosurgery (FSRS) and staged radiosurgery (SSRS) have been recently examined as alternative approaches for larger lesions to permit better tumor control without increased toxicity. CASE REPORT: We present the case of a patient who developed symptomatic radionecrosis in two brain metastasis, 2.3 cm and 2.1 cm in size, which were treated with 18 Gy in one fraction, but no radionecrosis in a 3.3 cm lesion treated in two fractions of 15 Gy nor in two punctate lesions that were treated in one fraction of 20 Gy. Although she did not respond to steroids, she responded to bevacizumab symptomatically and on neuroimaging. CONCLUSION: Congruent with other recent studies, our report suggests that large brain metastasis should be considered for FSRS/SSRS.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Encéfalo/efectos de la radiación , Fraccionamiento de la Dosis de Radiación , Radiocirugia/métodos , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Bevacizumab/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Femenino , Humanos , Necrosis/radioterapia , Resultado del Tratamiento
8.
J Vis Exp ; (168)2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33682858

RESUMEN

Parkinson's disease (PD) is a progressive disorder traditionally defined by resting tremor and akinesia, primarily due to loss of dopaminergic neurons in the substantia nigra. Affected brain areas display intraneuronal fibrillar inclusions consisting mainly of alpha-synuclein (asyn) proteins. No animal model thus far has recapitulated all characteristics of this disease. Here, we describe the use of stereotaxic injection to deliver chemicals, proteins, or viral vectors intracranially in order to mimic various aspects of PD. These methods are well-established and widely used throughout the PD field. Stereotaxic injections are incredibly flexible; they can be adjusted in concentration, age of animal used for injection, brain area targeted and in animal species used. Combinations of substances allow for rapid variations to assess treatments or alter severity of the pathology or behavioral deficits. By injecting toxins into the brain, we can mimic inflammation and/or a severe loss of dopaminergic neurons resulting in substantial motor phenotypes. Viral vectors can be used to transduce cells to mimic genetic or mechanistic aspects. Preformed fibrillar asyn injections best recapitulate the progressive phenotype over an extended period of time. Once these methods are established, it can be economical to generate a new model compared to creating a new transgenic line. However, this method is labor intensive as it requires 30 minutes to four hours per animal depending on the model used. Each animal will have a slightly different targeting and therefore create a diverse cohort which on one hand can be challenging to interpret results from; on the other hand, help mimic a more realistic diversity found in patients. Mistargeted animals can be identified using behavioral or imaging readouts, or only after being sacrificed leading to smallercohort size after the study has already been concluded. Overall, this method is a rudimentary but effective way to assess a diverse set of PD aspects.


Asunto(s)
Sistemas de Liberación de Medicamentos , Vectores Genéticos/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Técnicas Estereotáxicas , Virus/genética , Anestesia , Animales , Encéfalo/patología , Modelos Animales de Enfermedad , Humanos , Masculino , Cuidados Posoperatorios
9.
Nat Commun ; 12(1): 1490, 2021 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-33674568

RESUMEN

The brain of mammals lacks a significant ability to regenerate neurons and is thus particularly vulnerable. To protect the brain from injury and disease, damage control by astrocytes through astrogliosis and scar formation is vital. Here, we show that brain injury in mice triggers an immediate upregulation of the actin-binding protein Drebrin (DBN) in astrocytes, which is essential for scar formation and maintenance of astrocyte reactivity. In turn, DBN loss leads to defective astrocyte scar formation and excessive neurodegeneration following brain injuries. At the cellular level, we show that DBN switches actin homeostasis from ARP2/3-dependent arrays to microtubule-compatible scaffolds, facilitating the formation of RAB8-positive membrane tubules. This injury-specific RAB8 membrane compartment serves as hub for the trafficking of surface proteins involved in astrogliosis and adhesion mediators, such as ß1-integrin. Our work shows that DBN-mediated membrane trafficking in astrocytes is an important neuroprotective mechanism following traumatic brain injury in mice.


Asunto(s)
Astrocitos/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Cicatriz/metabolismo , Neuropéptidos/genética , Neuropéptidos/metabolismo , Complejo 2-3 Proteico Relacionado con la Actina , Actinas/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Lesiones Traumáticas del Encéfalo/patología , Movimiento Celular , Sistema Nervioso Central/metabolismo , Modelos Animales de Enfermedad , Gliosis/metabolismo , Gliosis/patología , Ratones , Ratones Noqueados , Neuroprotección , Transcriptoma , Proteínas de Unión al GTP rab/metabolismo
10.
Nat Commun ; 12(1): 1882, 2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33767197

RESUMEN

Single-cell RNA-sequencing (scRNA-Seq) is widely used to reveal the heterogeneity and dynamics of tissues, organisms, and complex diseases, but its analyses still suffer from multiple grand challenges, including the sequencing sparsity and complex differential patterns in gene expression. We introduce the scGNN (single-cell graph neural network) to provide a hypothesis-free deep learning framework for scRNA-Seq analyses. This framework formulates and aggregates cell-cell relationships with graph neural networks and models heterogeneous gene expression patterns using a left-truncated mixture Gaussian model. scGNN integrates three iterative multi-modal autoencoders and outperforms existing tools for gene imputation and cell clustering on four benchmark scRNA-Seq datasets. In an Alzheimer's disease study with 13,214 single nuclei from postmortem brain tissues, scGNN successfully illustrated disease-related neural development and the differential mechanism. scGNN provides an effective representation of gene expression and cell-cell relationships. It is also a powerful framework that can be applied to general scRNA-Seq analyses.


Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , RNA-Seq/métodos , Análisis de la Célula Individual/métodos , Transcriptoma/genética , Encéfalo/citología , Encéfalo/patología , Análisis por Conglomerados , Biología Computacional , Aprendizaje Profundo , Humanos , Secuenciación del Exoma Completo
11.
Int J Mol Sci ; 22(4)2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33671305

RESUMEN

Traumatic brain injuries (TBIs) are a significant health problem both in the United States and worldwide with over 27 million cases being reported globally every year. TBIs can vary significantly from a mild TBI with short-term symptoms to a moderate or severe TBI that can result in long-term or life-long detrimental effects. In the case of a moderate to severe TBI, the primary injury causes immediate damage to structural tissue and cellular components. This may be followed by secondary injuries that can be the cause of chronic and debilitating neurodegenerative effects. At present, there are no standard treatments that effectively target the primary or secondary TBI injuries themselves. Current treatment strategies often focus on addressing post-injury symptoms, including the trauma itself as well as the development of cognitive, behavioral, and psychiatric impairment. Additional therapies such as pharmacological, stem cell, and rehabilitative have in some cases shown little to no improvement on their own, but when applied in combination have given encouraging results. In this review, we will abridge and discuss some of the most recent research advances in stem cell therapies, advanced engineered biomaterials used to support stem transplantation, and the role of rehabilitative therapies in TBI treatment. These research examples are intended to form a multi-tiered perspective for stem-cell therapies used to treat TBIs; stem cells and stem cell products to mitigate neuroinflammation and provide neuroprotective effects, biomaterials to support the survival, migration, and integration of transplanted stem cells, and finally rehabilitative therapies to support stem cell integration and compensatory and restorative plasticity.


Asunto(s)
Lesiones Traumáticas del Encéfalo/rehabilitación , Lesiones Traumáticas del Encéfalo/terapia , Encéfalo/patología , Inflamación/patología , Inflamación/terapia , Trasplante de Células Madre , Células Madre/citología , Animales , Supervivencia Celular , Humanos
12.
Nat Commun ; 12(1): 1503, 2021 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-33686071

RESUMEN

Brain metastases are the most common tumor of the brain with a dismal prognosis. A fraction of patients with brain metastasis benefit from treatment with immune checkpoint inhibitors (ICI) and the degree and phenotype of the immune cell infiltration has been used to predict response to ICI. However, the anatomical location of brain lesions limits access to tumor material to characterize the immune phenotype. Here, we characterize immune cells present in brain lesions and matched cerebrospinal fluid (CSF) using single-cell RNA sequencing combined with T cell receptor genotyping. Tumor immune infiltration and specifically CD8+ T cell infiltration can be discerned through the analysis of the CSF. Consistently, identical T cell receptor clonotypes are detected in brain lesions and CSF, confirming cell exchange between these compartments. The analysis of immune cells of the CSF can provide a non-invasive alternative to predict the response to ICI, as well as identify the T cell receptor clonotypes present in brain metastasis.


Asunto(s)
Neoplasias Encefálicas/inmunología , Líquido Cefalorraquídeo/inmunología , Leucocitos , Microambiente Tumoral/inmunología , Adenocarcinoma del Pulmón , Encéfalo/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Linfocitos T CD8-positivos/inmunología , Humanos , Neoplasias Pulmonares , Pronóstico
13.
Int J Nanomedicine ; 16: 2203-2217, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33762821

RESUMEN

Background: It is well known that smoking is harmful to health; however, it can also ameliorate anxiety. To date, it is unclear whether any nanoparticles found in cigarette mainstream smoke (CS) contribute to this effect. Aim: The aim of this study was to assess the particle composition of CS to identify novel anti-anxiety components. Methods: Carbon dots (CDs) from CS (CS-CDs) were characterised using high-resolution transmission electron microscopy, Fourier-transform infrared, ultraviolet, fluorescence, X-ray photoelectron spectroscopy, X-ray diffraction and high-performance liquid chromatography. The anti-anxiety effects of CS-CDs in mouse models were evaluated and confirmed with the elevated plus maze and open-field tests. Results: The quantum yield of CS-CDs was 13.74%, with a composition of C, O, and N. In addition, the surface groups contained O-H, C-H, C=O, C-N, N-H, C-O-C, and COO- bonds. Acute toxicity testing revealed that CS-CDs had low in vitro and in vivo toxicity within a certain concentration range. The results of the elevated plus maze and open-field tests showed that CS-CDs had a significant anti-anxiety effect and a certain sedative effect in mice. The mechanism of these effects may be related to the decrease in glutamate levels and promotion of norepinephrine production in the mouse brain, and the decrease in dopamine in mouse serum due to CS-CDs. Conclusion: CS-CDs may have anti-anxiety and certain sedative effects. This study provides a new perspective for a more comprehensive understanding of the components, properties, and functions of CS. Furthermore, it offers a novel target for the development of smoking cessation treatments, such as nicotine replacement therapy.


Asunto(s)
Conducta Animal , Carbono/química , Fumar Cigarrillos/efectos adversos , Sistema Endocrino/metabolismo , Neurotransmisores/metabolismo , Puntos Cuánticos/química , Agua/química , Hormona Adrenocorticotrópica/sangre , Animales , Ansiedad/sangre , Ansiedad/patología , Encéfalo/metabolismo , Encéfalo/patología , Cromatografía Líquida de Alta Presión , Corticosterona/sangre , Hormona Liberadora de Corticotropina/sangre , Dopamina/sangre , Masculino , Ratones , Ratones Endogámicos ICR , Espectroscopía de Fotoelectrones , Puntos Cuánticos/ultraestructura , Células RAW 264.7 , Espectrometría de Fluorescencia , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Pruebas de Toxicidad Aguda , Difracción de Rayos X
14.
Nat Commun ; 12(1): 1647, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33712584

RESUMEN

Major depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.


Asunto(s)
Encéfalo/metabolismo , Encéfalo/patología , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/metabolismo , Transcriptoma , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Neuroimagen/métodos , Neuronas
15.
Hum Immunol ; 82(3): 155-161, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33583639

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to neuronal death in the brain and spinal cord. Over the last decades, evidence has emerged regarding the functional diversity of astrocytes, microglia, and T cells in the central nervous system (CNS), and the role of neuroinflammation in ALS. In this review, we summarize current knowledge regarding neuroinflammation in ALS, both at the level of specific molecular pathways and potential cellular pathways as well as outline questions about the immune mechanisms involved in ALS pathogenesis.


Asunto(s)
Esclerosis Amiotrófica Lateral/inmunología , Encéfalo/patología , Neuroglía/inmunología , Neuronas/patología , Médula Espinal/patología , Linfocitos T/inmunología , Animales , Autoinmunidad , Humanos , Inmunidad Celular , Inflamación Neurogénica , Transducción de Señal
16.
Nat Neurosci ; 24(3): 312-325, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33589835

RESUMEN

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.


Asunto(s)
Envejecimiento/patología , Astrocitos/patología , Encéfalo/patología , Médula Espinal/patología , Animales , Encefalopatías/patología , Lesiones Encefálicas/patología , Humanos , Traumatismos de la Médula Espinal/patología
17.
BMC Neurol ; 21(1): 77, 2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33596839

RESUMEN

BACKGROUND: Cerebral radiation injury, including subacute radiation reactions and later stage radiation necrosis, is a severe side effect of brain tumor radiotherapy. A protocol of four infusions of the monoclonal antibody bevacizumab has been shown to be a highly effective treatment. However, bevacizumab is costly and can cause severe complications including thrombosis, bleeding and gastrointestinal perforations. METHODS: We performed a retrospective analysis of patients treated in our clinic for cerebral radiation injury who received only a singular treatment with bevacizumab. Single-shot was defined as a singular administration of bevacizumab without a second administration during an interval of at least 6 weeks. RESULTS: We identified 11 patients who had received a singular administration of bevacizumab to treat cerebral radiation injury. Prior radiation had been administered to treat gliomas (ten patients) or breast cancer brain metastases (one patient). 9 of 10 patients with available MRIs showed a marked reduction of edema at first follow-up. Discontinuation of Dexamethasone was possible in 6 patients and a significant dose reduction could be achieved in all other patients. One patient developed pulmonary artery embolism 2 months after bevacizumab administration. The median time to treatment failure of any cause was 3 months. CONCLUSIONS: Single-shot bevacizumab therefore has meaningful activity in cerebral radiation injury, but durable control is rarely achieved. In patients where a complete protocol of four infusions with bevacizumab is not feasible due to medical contraindications or lack of reimbursement, single-shot bevacizumab treatment may be considered.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Bevacizumab/administración & dosificación , Edema Encefálico/tratamiento farmacológico , Lesiones Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Encéfalo/patología , Traumatismos por Radiación/tratamiento farmacológico , Adulto , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Bevacizumab/uso terapéutico , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Lesiones Encefálicas/diagnóstico por imagen , Lesiones Encefálicas/etiología , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Dexametasona/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Glioma/radioterapia , Glucocorticoides/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Necrosis , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
18.
Neurology ; 96(11): e1491-e1500, 2021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-33568538

RESUMEN

OBJECTIVE: To examine whether amyloid PET in cognitively normal (CN) individuals screened for the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) study differed across self-identified non-Hispanic White and Black (NHW and NHB) groups. METHODS: We examined 3,689 NHW and 144 NHB participants who passed initial screening for the A4 study and underwent amyloid PET. The effect of race on amyloid PET was examined using logistic (dichotomous groups) and linear (continuous values) regression controlling for age, sex, and number of APOE ε4 and APOE ε2 alleles. Associations between amyloid and genetically determined ancestry (reflecting African, South Asian, East Asian, American, and European populations) were tested within the NHB group. Potential interactions with APOE were assessed. RESULTS: NHB participants had lower rates of amyloid positivity and lower continuous amyloid levels compared to NHW participants. This race effect on amyloid was strongest in the APOE ε4 group. Within NHB participants, those with a lower percentage of African ancestry had higher amyloid. A greater proportion of NHB participants did not pass initial screening compared to NHW participants, suggesting potential sources of bias related to race in the A4 PET data. CONCLUSION: Reduced amyloid was observed in self-identified NHB participants who passed initial eligibility criteria for the A4 study. This work stresses the importance of investigating AD biomarkers in ancestrally diverse samples as well as the need for careful consideration regarding study eligibility criteria in AD prevention trials.


Asunto(s)
Enfermedad de Alzheimer/etnología , Enfermedad de Alzheimer/patología , Proteínas Amiloidogénicas/metabolismo , Encéfalo/patología , Afroamericanos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Proteínas Amiloidogénicas/análisis , Apolipoproteínas E/genética , Biomarcadores/análisis , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Masculino , Tomografía de Emisión de Positrones , Estados Unidos
19.
Yonsei Med J ; 62(3): 255-261, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33635016

RESUMEN

PURPOSE: This study aimed to examine the inter-method reliability and volumetric differences between NeuroQuant (NQ) and Freesurfer (FS) using T1 volume imaging sequence with different slice thicknesses in patients with mild cognitive impairment (MCI). MATERIALS AND METHODS: This retrospective study enrolled 80 patients diagnosed with MCI at our memory clinic. NQ and FS were used for volumetric analysis of three-dimensional T1-weighted images with slice thickness of 1 and 1.2 mm. Inter-method reliability was measured with Pearson correlation coefficient (r), intraclass correlation coefficient (ICC), and effect size (ES). RESULTS: Overall, NQ volumes were larger than FS volumes in several locations: whole brain (0.78%), cortical gray matter (5.34%), and white matter (2.68%). Volume measures by NQ and FS showed good-to-excellent ICCs with both 1 and 1.2 mm slice thickness (ICC=0.75-0.97, ES=-1.0-0.73 vs. ICC=0.78-0.96, ES=-0.9-0.77, respectively), except for putamen, pallidum, thalamus, and total intracranial volumes. The ICCs in all locations, except the putamen and cerebellum, were slightly higher with a slice thickness of 1 mm compared to those of 1.2 mm. CONCLUSION: Inter-method reliability between NQ and FS was good-to-excellent in most regions with improvement with a 1-mm slice thickness. This finding indicates that the potential effects of slice thickness should be considered when performing volumetric measurements for cognitive impairment.


Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/patología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Imagen por Resonancia Magnética , Anciano , Anciano de 80 o más Años , Automatización , Femenino , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos
20.
J Vis Exp ; (167)2021 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-33554966

RESUMEN

It has been well studied that the EcoHIV infected mouse model is of significant utility in investigating HIV associated neurological complications. Establishment of the EcoHIV infected rat model for studies of drug abuse and neurocognitive disorders, would be beneficial in the study of neuroHIV and HIV-1 associated neurocognitive disorders (HAND). In the present study, we demonstrate the successful creation of a rat model of active HIV infection using chimeric HIV (EcoHIV). First, the lentiviral construct of EcoHIV was packaged in cultured 293 FT cells for 48 hours. Then, the conditional medium was concentrated and titered. Next, we performed bilateral stereotaxic injections of the EcoHIV-EGFP into F344/N rat brain tissue. One week after infection, EGFP fluorescence signals were detected in the infected brain tissue, indicating that EcoHIV successfully induces an active HIV infection in rats. In addition, immunostaining for the microglial cell marker, Iba1, was performed. The results indicated that microglia were the predominant cell type harboring EcoHIV. Furthermore, EcoHIV rats exhibited alterations in temporal processing, a potential underlying neurobehavioral mechanism of HAND as well as synaptic dysfunction eight weeks after infection. Collectively, the present study extends the EcoHIV model of HIV-1 infection to the rat offering a valuable biological system to study HIV-1 viral reservoirs in the brain as well as HAND and associated comorbidities such as drug abuse.


Asunto(s)
Encéfalo/patología , Encéfalo/virología , Infecciones por VIH/patología , VIH-1/fisiología , Animales , Quimera , Espinas Dendríticas/patología , Modelos Animales de Enfermedad , Proteínas Fluorescentes Verdes/metabolismo , Infecciones por VIH/complicaciones , Humanos , Masculino , Ratones , Ratas Endogámicas F344 , Técnicas Estereotáxicas , Sinapsis/patología , Factores de Tiempo , Replicación Viral
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