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1.
J Headache Pain ; 22(1): 4, 2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-33413090

RESUMEN

BACKGROUND: The moment-to-moment variability of resting-state brain activity has been suggested to play an active role in chronic pain. Here, we investigated the regional blood-oxygen-level-dependent signal variability (BOLDSV) and inter-regional dynamic functional connectivity (dFC) in the interictal phase of migraine and its relationship with the attack severity. METHODS: We acquired resting-state functional magnetic resonance imaging from 20 migraine patients and 26 healthy controls (HC). We calculated the standard deviation (SD) of the BOLD time-series at each voxel as a measure of the BOLD signal variability (BOLDSV) and performed a whole-brain voxel-wise group comparison. The brain regions showing significant group differences in BOLDSV were used to define the regions of interest (ROIs). The SD and mean of the dynamic conditional correlation between those ROIs were calculated to measure the variability and strength of the dFC. Furthermore, patients' experimental pain thresholds and headache pain area/intensity levels during the migraine ictal-phase were assessed for clinical correlations. RESULTS: We found that migraineurs, compared to HCs, displayed greater BOLDSV in the ascending trigeminal spinal-thalamo-cortical pathways, including the spinal trigeminal nucleus, pulvinar/ventral posteromedial (VPM) nuclei of the thalamus, primary somatosensory cortex (S1), and posterior insula. Conversely, migraine patients exhibited lower BOLDSV in the top-down modulatory pathways, including the dorsolateral prefrontal (dlPFC) and inferior parietal (IPC) cortices compared to HCs. Importantly, abnormal interictal BOLDSV in the ascending trigeminal spinal-thalamo-cortical and frontoparietal pathways were associated with the patient's headache severity and thermal pain sensitivity during the migraine attack. Migraineurs also had significantly lower variability and greater strength of dFC within the thalamo-cortical pathway (VPM-S1) than HCs. In contrast, migraine patients showed greater variability and lower strength of dFC within the frontoparietal pathway (dlPFC-IPC). CONCLUSIONS: Migraine is associated with alterations in temporal signal variability in the ascending trigeminal somatosensory and top-down modulatory pathways, which may explain migraine-related pain and allodynia. Contrasting patterns of time-varying connectivity within the thalamo-cortical and frontoparietal pathways could be linked to abnormal network integrity and instability for pain transmission and modulation.


Asunto(s)
Imagen por Resonancia Magnética , Trastornos Migrañosos , Encéfalo/diagnóstico por imagen , Humanos , Hiperalgesia , Trastornos Migrañosos/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagen , Dolor
2.
BMC Public Health ; 21(1): 126, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33435943

RESUMEN

BACKGROUND: Air pollution has been linked to increased mortality and morbidity. The Program 4 of the Healthy Aging in Industrial Environment study investigates whether the health and wellbeing benefits of physical activity (PA) can be fully realized in individuals living in highly polluted environments. Herein, we introduce the behavioral, psychological and neuroimaging protocol of the study. METHODS: This is a prospective cohort study of N = 1500 individuals aged 18-65 years comparing: (1) individuals living in the highly polluted, industrial region surrounding the city of Ostrava (n = 750), and (2) controls from the comparison region with relative low pollution levels in Southern Bohemia (n = 750). Quota sampling is used to obtain samples balanced on age, gender, PA status (60% active runners vs. 40% insufficiently active). Participants are screened and complete baseline assessments through online questionnaires and in-person lab-based assessments of physiological, biomechanical, neuroimaging and cognitive function parameters. Prospective 12-month intensive monitoring of air pollution and behavioral parameters (PA, inactivity, and sleep) follows, with a focus on PA-related injuries and psychological factors through fitness trackers, smartphones, and mobile apps. Subsequently, there will be a 5-year follow-up of the study cohort. DISCUSSION: The design of the study will allow for (1) the assessment of both short-term variation and long-term change in behavioral parameters, (2) evaluation of the incidence of musculoskeletal injuries and psychological factors impacting behavior and injury recovery, and (3) the impact that air pollution status (and change) has on behavior, psychological resilience, and injury recovery. Furthermore, the integration of MRI techniques and cognitive assessment in combination with data on behavioral, biological and environmental variables will provide an opportunity to examine brain structure and cognitive function in relation to health behavior and air pollution, as well as other factors affecting resilience against and vulnerability to adverse changes in brain structure and cognitive aging. This study will help inform individuals about personal risk factors and decision-makers about the impact of environmental factors on negative health outcomes and potential underlying biological, behavioral and psychological mechanisms. Challenges and opportunities stemming from the timing of the study that coincided with the COVID-19 pandemic are also discussed.


Asunto(s)
Contaminación del Aire/efectos adversos , Ejercicio Físico , Adolescente , Adulto , Anciano , Contaminantes Atmosféricos/análisis , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Cognición/fisiología , Femenino , Conductas Relacionadas con la Salud , Envejecimiento Saludable , Humanos , Masculino , Persona de Mediana Edad , Neuroimagen , Estudios Prospectivos , Pirimidinas/química , Proyectos de Investigación , Resiliencia Psicológica , Encuestas y Cuestionarios , Adulto Joven
3.
Nat Commun ; 12(1): 216, 2021 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-33431849

RESUMEN

While a number of human coronaviruses are believed to be originated from ancestral viruses in bats, it remains unclear if bat coronaviruses are ready to cause direct bat-to-human transmission. Here, we report the isolation of a MERS-related coronavirus, Tylonycteris-bat-CoV-HKU4, from lesser bamboo bats. Tylonycteris-bat-CoV-HKU4 replicates efficiently in human colorectal adenocarcinoma and hepatocarcinoma cells with cytopathic effects, and can utilize human-dipeptidyl-peptidase-4 and dromedary camel-dipeptidyl-peptidase-4 as the receptors for cell entry. Flow cytometry, co-immunoprecipitation and surface plasmon resonance assays show that Tylonycteris-bat-CoV-HKU4-receptor-binding-domain can bind human-dipeptidyl-peptidase-4, dromedary camel-dipeptidyl-peptidase-4, and Tylonycteris pachypus-dipeptidyl-peptidase-4. Tylonycteris-bat-CoV-HKU4 can infect human-dipeptidyl-peptidase-4-transgenic mice by intranasal inoculation with self-limiting disease. Positive virus and inflammatory changes were detected in lungs and brains of infected mice, associated with suppression of antiviral cytokines and activation of proinflammatory cytokines and chemokines. The results suggest that MERS-related bat coronaviruses may overcome species barrier by utilizing dipeptidyl-peptidase-4 and potentially emerge in humans by direct bat-to-human transmission.


Asunto(s)
Quirópteros/virología , Infecciones por Coronavirus/virología , Dipeptidil Peptidasa 4/metabolismo , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Animales , Encéfalo/patología , Células CACO-2 , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/transmisión , Citocinas/metabolismo , Dipeptidil Peptidasa 4/genética , Células HEK293 , Especificidad del Huésped , Humanos , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética
4.
Bratisl Lek Listy ; 122(1): 24-27, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33393316

RESUMEN

OBJECTIVE: Cerebral microdialysis (CMD) is a method used to measure the concentration of metabolites and glycerol in the interstitium of the brain. The aim of this study was to investigate the effect of parenterally applied medication and nutrition containing external free glycerol (EFG) on cerebral values of glycerol in patients monitored and treated for non-traumatic subarachnoid hemorrhage (SAH). METHODS: In 13 patients, the values of CG concentrations were measured using CMD. The amounts of parenterally applied EFG (in hourly intervals) were calculated from patient records. All data were gathered retrospectively. To analyze the association between the parameters of interest and their relationship, Spearman´s correlation and p-values were calculated. RESULTS: There was no evident relationship between the CG and EFG concentrations when the dataset was analyzed as a whole (r = -0.146). However, when the analysis was applied to single patients, a varying degree of correlations was discovered in 7 patients (r = 0.431-0.867). CONCLUSION: The possible effect of externally administered glycerol contained in pharmaceuticals and nutrition on its brain concentrations must be considered when interpreting data of CMD (Tab. 2, Fig. 4,Ref. 16) Keywords: glycerol, microdialysis, brain, subarachnoid hemorrhage.


Asunto(s)
Encéfalo , Glicerol , Humanos , Microdiálisis , Estudios Retrospectivos , Hemorragia Subaracnoidea
5.
Bratisl Lek Listy ; 122(1): 39-44, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33393319

RESUMEN

OBJECTIVES: Our study aimed to investigate neurological symptoms in patients with COVID-19 and contribute to this area of limited knowledge. BACKGROUND: Increasing evidence shows that neurotropism is a common feature of Coronaviruses (CoVs). Like the other CoVs, SARS-CoV 2 uses angiotensin-converting enzyme 2 (ACE2). The brain is thought to express ACE2 receptors detected on glial cells and neurons. There are also ACE2 receptors in skeletal muscles. Our study aimed to investigate neurological symptoms in patients with COVID-19 and contribute to this area of limited knowledge. METHODS: A total of 51 patients, presented to hospitalized in our hospital between March 23, 2020 and April 16, 2020 were included in the study. The diagnosis of all patients included in the study was made according to the WHO interim guideline. The patients were divided into two subgroups as mild and severe course according to the severity of the disease. RESULTS: Neurological symptoms were detected in 16 (31.37 %) patients. Muscle injury was detected in 10 (19.61 %) patients. The most common neurological symptom was headache (n: 9, 17.65 %). When the frequency of all neurological symptoms was compared in those with severe and mild disease, no significant differences were found between the groups. When the frequency of muscular involvement was compared in patients with severe and mild course, no significant differences were found between the groups. CONCLUSION: The nervous system and skeletal muscle system may be among viral targets. Detection of some neurological findings may be valuable in predicting the course of the disease. Some laboratory values can allow predicting disease severity and neurological symptoms (Tab. 5, Ref. 23) Keywords: COVID-19, neurotropism, muscle injury, headache.


Asunto(s)
Encéfalo , Enfermedades del Sistema Nervioso Central , Cefalea , Humanos
6.
Ecotoxicol Environ Saf ; 208: 111747, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396073

RESUMEN

Residues of the psychoactive drug diazepam (DZP) may pose potential risks to fish in aquatic environments, especially by disrupting their behavioral traits. In this study, female and male zebrafish were subjected to chronic exposure (21 days) to sublethal doses (120 and 12 µg/L) of DZP, aimed to compare the characteristics of their behavioral responses to DZP exposure, and to investigate the possible links between those behavioral responses and variations in their brain γ-aminobutyric acid (GABA) and acetylcholinesterase (AChE) levels. Chronic exposure to DZP significantly decreased the swimming velocity and locomotor activity of both genders, indicating a typical sedative effect. Compared with males, whose locomotor activity was only significantly decreased by exposure to DZP for 21 days, females became hypoactive on day 14 (i.e., more sensitive), and they developed tolerance to the hypoactive effect induced by 120 µg/L DZP by day 21. Exposure to DZP significantly disturbed the behavioral traits related to social interactions in females but not in males. Those results indicate that DZP exhibits sex-dependent effects on the behaviors of fish. Moreover, exposure to DZP for 21 days significantly disturbed almost all of the tested behavioral traits associated with courtship when both genders were put together. Sex-dependent responses in brain GABA and AChE levels due to DZP exposure were also identified. Significant relationships between the brain GABA/AChE levels and some behavioral parameters related to locomotor activity were detected in females, but not in males.


Asunto(s)
Diazepam/toxicidad , Pruebas de Toxicidad Crónica , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/fisiología , Acetilcolinesterasa/metabolismo , Animales , Encéfalo/efectos de los fármacos , Diazepam/administración & dosificación , Femenino , Masculino , Actividad Motora/efectos de los fármacos , Natación , Pez Cebra/metabolismo , Ácido gamma-Aminobutírico/farmacología
7.
Nat Commun ; 12(1): 105, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397973

RESUMEN

Environmental triggers have important functions in multiple sclerosis (MS) susceptibility, phenotype, and trajectory. Exposure to early life trauma (ELT) has been associated with higher relapse rates in MS patients; however, the underlying mechanisms are not well-defined. Here we show ELT induces mechanistic and phenotypical alterations during experimental autoimmune encephalitis (EAE). ELT sustains downregulation of immune cell adrenergic receptors, which can be attributed to chronic norepinephrine circulation. ELT-subjected mice exhibit interferon-ß resistance and neurodegeneration driven by lymphotoxin and CXCR2 involvement. These phenotypic changes are observed in control EAE mice treated with ß1 adrenergic receptor antagonist. Conversely, ß1 adrenergic receptor agonist treatment to ELT mice abrogates phenotype changes via restoration of immune cell ß1 adrenergic receptor function. Our results indicate that ELT alters EAE phenotype via downregulation of ß1 adrenergic signaling in immune cells. These results have implications for the effect of environmental factors in provoking disease heterogeneity and might enable prediction of long-term outcomes in MS.


Asunto(s)
Regulación hacia Abajo , Interferón beta/metabolismo , Esclerosis Múltiple/complicaciones , Degeneración Nerviosa/complicaciones , Receptores Adrenérgicos beta 1/metabolismo , Transducción de Señal , Estrés Psicológico/complicaciones , Agonistas de Receptores Adrenérgicos beta 1/farmacología , Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Animales , Biomarcadores/metabolismo , Encéfalo/inmunología , Encéfalo/patología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/sangre , Encefalomielitis Autoinmune Experimental/patología , Femenino , Aparato de Golgi/metabolismo , Masculino , Ratones Endogámicos C57BL , Esclerosis Múltiple/sangre , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Degeneración Nerviosa/sangre , Degeneración Nerviosa/inmunología , Degeneración Nerviosa/patología , Neuronas/metabolismo , Neuronas/patología , Norepinefrina/sangre , Fenotipo , Índice de Severidad de la Enfermedad , Regulación hacia Arriba/efectos de los fármacos
8.
Nat Commun ; 12(1): 107, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33398061

RESUMEN

Rapid 3D imaging of entire organs and organisms at cellular resolution is a recurring challenge in life science. Here we report on a computational light-sheet microscopy able to achieve minute-timescale high-resolution mapping of entire macro-scale organs. Through combining a dual-side confocally-scanned Bessel light-sheet illumination which provides thinner-and-wider optical sectioning of deep tissues, with a content-aware compressed sensing (CACS) computation pipeline which further improves the contrast and resolution based on a single acquisition, our approach yields 3D images with high, isotropic spatial resolution and rapid acquisition over two-order-of-magnitude faster than conventional 3D microscopy implementations. We demonstrate the imaging of whole brain (~400 mm3), entire gastrocnemius and tibialis muscles (~200 mm3) of mouse at ultra-high throughput of 5~10 min per sample and post-improved subcellular resolution of ~ 1.5 µm (0.5-µm iso-voxel size). Various system-level cellular analyses, such as mapping cell populations at different brain sub-regions, tracing long-distance projection neurons over the entire brain, and calculating neuromuscular junction occupancy across whole muscle, are also readily accomplished by our method.


Asunto(s)
Imagenología Tridimensional , Microscopía Fluorescente/métodos , Especificidad de Órganos , Animales , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Recuento de Células , Proteínas Fluorescentes Verdes/metabolismo , Ratones , Músculos/diagnóstico por imagen , Unión Neuromuscular/diagnóstico por imagen , Neuronas/metabolismo , Fracciones Subcelulares
9.
Eur J Neurol ; 28(1): 248-258, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32853434

RESUMEN

BACKGROUND AND PURPOSE: Neurological manifestations in coronavirus disease (COVID)-2019 may adversely affect clinical outcomes. Severe COVID-19 and uremia are risk factors for neurological complications. However, the lack of insight into their pathogenesis, particularly with respect to the role of the cytokine release syndrome (CRS), is currently hampering effective therapeutic interventions. The aims of this study were to describe the neurological manifestations of patients with COVID-19 and to gain pathophysiological insights with respect to CRS. METHODS: In this longitudinal study, we performed extensive clinical, laboratory and imaging phenotyping in five patients admitted to our renal unit. RESULTS: Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Notably, neurological disturbances were accompanied by laboratory evidence of CRS. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was undetectable in the cerebrospinal fluid (CSF). Hyperalbuminorrachia and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain magnetic resonance imaging findings comprised evidence of acute leukoencephalitis (n = 3, one of whom had a hemorrhagic form), cytotoxic edema mimicking ischaemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted, resulting in rapid recovery from neurological disturbances in two cases. SARS-CoV2 was undetectable in 88 of the 90 patients with COVID-19 who underwent Reverse Transcription-PCR testing of CSF. CONCLUSIONS: Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory and imaging similarities with those of chimeric antigen receptor T-cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.


Asunto(s)
Encefalopatías/etiología , Síndrome de Liberación de Citoquinas/etiología , Corticoesteroides/uso terapéutico , Anciano , Barrera Hematoencefálica/fisiopatología , Encéfalo/diagnóstico por imagen , Encefalopatías/fisiopatología , Edema Encefálico/etiología , /fisiopatología , Síndrome de Liberación de Citoquinas/metabolismo , Síndrome de Liberación de Citoquinas/fisiopatología , Femenino , Humanos , Inmunoglobulinas/uso terapéutico , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/fisiopatología , Resultado del Tratamiento
10.
Clin Nucl Med ; 46(2): 136-137, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33208611

RESUMEN

ABSTRACT: A 64-year-old man with primary progressive multiple sclerosis (Expanded Disability Status Scale 3.5) underwent PET using 18F-PBR06, a second-generation 18-kDa translocator protein ligand targeting activated brain microglia and astrocytes. Voxel-by-voxel statistical comparison of patient's PET images (acquired 60-90 minutes postinjection) with a healthy control data set was performed to generate a 3-dimensional z-score map of increased radiotracer uptake, which showed widespread increased glial activation in normal-appearing cerebral white matter, white matter lesional and perilesional areas, brainstem and cerebellum. In contrast, patient's 3-T MRI scan showed only a few small white matter brain lesions without contrast enhancement.


Asunto(s)
Acetanilidas , Esclerosis Múltiple Crónica Progresiva/diagnóstico por imagen , Esclerosis Múltiple Crónica Progresiva/patología , Neuroglía/patología , Tomografía de Emisión de Positrones , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Estudios de Factibilidad , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/metabolismo
11.
APMIS ; 129(2): 37-54, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33098147

RESUMEN

Coronaviridae family includes pathogen viruses for humans, that lead to clinical conditions with main respiratory involvement; many of these viruses have notoriously a neuroinvasive potential, as demonstrated by published data on SARS-CoV and MERS-CoV epidemics, as well by results obtained in experimental models. During pandemic of coronavirus disease 2019 (COVID-19), it is noticed that the central nervous system involvement represented a truly significant moment in the history of some COVID-19 patients; indeed, clinical and radiological features published in literature regarding COVID-19 disease are consistent with a neurological involvement. It is also known that histopathological data related to SARS-CoV2 infection have been published with considerable delay, which was even greater for neuropathological information. Moreover, many published data are incomplete, and often the lesions described are not directly related to the action of the virus. In this review, we collected the available radiological and neuropathological information, in order to delineate a more complete picture of the relationship between SARS-Cov2 and brain, focusing our attention on the two most important neuroinvasion routes for the virus. We also highlighted what we consider methodological mistakes both in the autopsy procedures and brain study in COVID-19 deaths. We emphasize the need for a complete study of all the organs in case of autopsy. It is important that through this experience, we no longer do the mistake of neglecting the brain.


Asunto(s)
Encéfalo/patología , Enfermedades del Sistema Nervioso/patología , Ageusia/virología , Encéfalo/virología , Humanos , Enfermedades del Sistema Nervioso/virología , Traumatismos del Nervio Olfatorio/virología , Síndrome Respiratorio Agudo Grave/patología , Síndrome Respiratorio Agudo Grave/virología
12.
Artículo en Inglés | MEDLINE | ID: mdl-33186710

RESUMEN

In 2009, Dr. Anthony Fauci stated, "The 1918-1919 influenza pandemic was a defining event in the history of public health."1 In 2020, a popular medical website suggested that the 1918 pandemic may offer "lasting lessons for the world in the grip of COVID-19."2 One lesson from the 1918 pandemic relates to residual long-term effects. In his influential book published in 1971, Minimal Brain Dysfunction in Children, Wender3 reviewed historical accounts of the 1918 pandemic and suggested that viral infection had selective brain effects on catecholamine nuclei, and behavioral sequelae in some children emerged and overlapped with symptoms that now define attention-deficit/hyperactivity disorder (ADHD), and behavioral sequelae emerged in some adults that overlapped with symptoms of Parkinson's disease. Based on this and several excitotoxic models of behavioral disorders (ie, Volpe, Altman, Amsel, Benveniste, and Lou) related to arterial architecture and patterns of blood flow to the brain, previously our group4 proposed etiologic subtypes of ADHD based on a dopamine-deficit hypothesis and assumption that dopamine neurons might be particularly sensitive to a variety of environmental insults. We speculate that residual effects of 2019 novel coronavirus disease (COVID-19) may selectively affect brain regions underlying attention and motivation deficits associated with ADHD, as documented by positron emission tomography imaging studies of adults (see Volkow et al.5), which could increase risk for an infection-triggered etiologic subtype of ADHD.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Adulto , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/etiología , Encéfalo/diagnóstico por imagen , Niño , Humanos , Pandemias
13.
Neurology ; 96(1): e81-e92, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33093220

RESUMEN

OBJECTIVE: To determine the associations between amyloid-PET, tau-PET, and atrophy with the behavioral/dysexecutive presentation of Alzheimer disease (AD), how these differ from amnestic AD, and how they correlate to clinical symptoms. METHODS: We assessed 15 patients with behavioral/dysexecutive AD recruited from a tertiary care memory clinic, all of whom had biologically defined AD. They were compared with 25 patients with disease severity- and age-matched amnestic AD and a group of 131 cognitively unimpaired (CU) elderly individuals. All participants were evaluated with amyloid-PET with [18F]AZD4694, tau-PET with [18F]MK6240, MRI, and neuropsychological testing. RESULTS: Voxelwise contrasts identified patterns of frontal cortical tau aggregation in behavioral/dysexecutive AD, with peaks in medial prefrontal, anterior cingulate, and frontal insular cortices in contrast to amnestic AD. No differences were observed in the distribution of amyloid-PET or atrophy as determined by voxel-based morphometry. Voxelwise area under the receiver operating characteristic curve analyses revealed that tau-PET uptake in the medial prefrontal, anterior cingulate, and frontal insular cortices were best able to differentiate between behavioral/dysexecutive and amnestic AD (area under the curve 0.87). Voxelwise regressions demonstrated relationships between frontal cortical tau load and degree of executive dysfunction. CONCLUSIONS: Our results provide evidence of frontal cortical involvement of tau pathology in behavioral/dysexecutive AD and highlight the need for consensus clinical criteria in this syndrome.


Asunto(s)
Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Encéfalo/patología , Trastornos Mentales/patología , Proteínas tau/metabolismo , Anciano , Enfermedad de Alzheimer/complicaciones , Atrofia/patología , Femenino , Humanos , Masculino , Trastornos Mentales/etiología , Persona de Mediana Edad , Neuroimagen/métodos , Fenotipo
14.
Life Sci ; 264: 118631, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33131748

RESUMEN

AIMS: Traumatic brain injury (TBI) is a common nervous system injury. However, the detailed mechanisms about functional dysregulation and dignostic biomarkers post-TBI are still unclear. So we aimed to identify potential differentially expressed proteins and genes in TBI for clinical diagnosis and therapeutic purposes. MAIN METHODS: Rat TBI model was established by the weight-drop method. First, through TMT-proteomics, we screened for the change in the proteins expression profile acute phase post-TBI. The DAVID and Reactome databases were used to analyze and visualize the dysregulation proteins. Then, using publicly available microarray datasets GSE45997, differentially expressed genes (DGEs) were identified for the 24 h post-TBI stage. Also, the proteomic data were compared with microarray data to analyze the similarity. KEY FINDINGS: We found significant proteomics and transcriptomic changes in post-TBI samples. 989, 881, 832, 1057 proteins were quantitated at 1 h, 6 h, 24 h, and 3 d post-injury correspondingly. Concerning proteomics findings, oxygen transport, acute-phase response, and negative regulation of endopeptidase activity were influenced throughout the acute phrase of TBI. Also, pathways related to scavenging of heme from plasma, binding, and uptake of ligands by scavenger receptors were highly enriched in all time-points of TBI samples. SIGNIFICANCE: We noticed that the interaction-networks trend to get complicated with more node connections following the progression of TBI. We inferred that Hk-1, PRKAR2A, and MBP could be novel candidate biomarkers related to time-injury in acute-phase TBI. Also, Ceruloplasmin and Complement C3 were found to be important proteins and genes are involved in the TBI.


Asunto(s)
Biomarcadores/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Proteómica/métodos , Animales , Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/diagnóstico , Biología Computacional , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Oxígeno/metabolismo , Proteoma , Ratas , Ratas Sprague-Dawley , Transcriptoma
15.
Life Sci ; 264: 118626, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33148417

RESUMEN

AIMS: Circular RNAs (circRNAs) have been shown to play crucial roles in various biological processes and human diseases. However, their exact functions in ischemic stroke remain largely unknown. In this study, we explored the functional role of circRNA HECTD1 (circ-HECTD1) and its underlying mechanism in cerebral ischemia/reperfusion injury. METHODS: Mouse middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation (OGD) model in HT22 cells were used to mimic the cerebral ischemia/reperfusion injury. Brain infarct volume, flow cytometry, caspase 3 activity, NF-κB activity, and TUNEL staining were performed to evaluate the function of circ-HECTD1. Luciferase report assay was used to explore the regulatory mechanism. FINDINGS: The results showed that the expression of circ-HECTD1 and tumor necrosis factor receptor-associated factor 3 (TRAF3) was remarkably up-regulated, while miR-133b was down-regulated in oxygen-glucose deprivation (OGD)-induced HT22 cells and mouse middle cerebral artery occlusion (MCAO) model. circ-HECTD1 knockdown relieved OGD-caused neuronal cell death in vitro. Simultaneously, circ-HECTD1 knockdown improved cerebral infarction volume and neuronal apoptosis in MCAO mice. circ-HECTD1 was able to negatively regulate the expression of miR-133b, and TRAF3 is one of the targets of miR-133b. Upregulation of miR-133b inhibited the expression of TRAF3 in OGD-stimulated cells, whereas circ-HECTD1 upregulation reversed this effect. Furthermore, upregulation of miR-133 was able to inhibit OGD-caused cell apoptosis and NF-κB activation, whereas upregulation of circ-HECTD1 attenuated these effects of miR-133b mimics. SIGNIFICANCE: Taken together, circ-HECTD1 knockdown inhibited the expression of TRAF3 by targeting miR-133b, thereby attenuating neuronal injury caused by cerebral ischemia.


Asunto(s)
/genética , MicroARNs/genética , Neuronas/patología , ARN Circular/genética , Factor 3 Asociado a Receptor de TNF/genética , Ubiquitina-Proteína Ligasas/genética , Animales , Apoptosis , Glucemia/metabolismo , Encéfalo/patología , Isquemia Encefálica/patología , Caspasa 3/metabolismo , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Masculino , Ratones , Ratones Endogámicos C57BL , Arteria Cerebral Media/patología , Neuroprotección , Oxígeno/metabolismo , Daño por Reperfusión/patología
16.
Life Sci ; 264: 118627, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33169684

RESUMEN

Gut microbiota represents a diverse and dynamic population of microorganisms harboring the gastrointestinal tract, which influences the host health and disease. Gut microbiota communicates with the brain and vice versa through complex bidirectional communication systems - the gut-brain axis, which integrates the peripheral intestinal function with emotional and cognitive brain centers via neuro-immuno-endocrine mediators. Aging alters the gut microbial population, which not only leads to gastrointestinal disturbances but also causes central nervous system (CNS) disorders such as dementia. Alzheimer's disease (AD) is the most common form of dementia affecting the older person, characterized by beta-amyloid (Aß) plaques and neurofibrillary tangles leading to the cognitive deficit and memory impairment. Multiple experimental and clinical studies revealed the role of gut microbiota in host cognition, and its dysbiosis associated with aging leads to neurodegeneration. Gut microbial dysbiosis leads to the secretion of amyloid and lipopolysaccharides (LPS), which disturbs the gastrointestinal permeability and blood-brain barrier. Thereby modulates the inflammatory signaling pathway promoting neuroinflammation, neuronal injury, and ultimately leading to neuronal death in AD. A recent study revealed the antimicrobial property of Aß peptide as an innate immune response against pathogenic microbes. Another study showed that bacterial amyloid shares molecular mimicry with Aß peptide, which elicits misfolding and aggregation of Aß peptide, it's seeding, and propagation through the gut-brain axis followed by microglial cell activation. As aging together with poor diet and gut-derived inflammatory response due to dysbiosis contributes to the pathogenesis of AD, modification of gut microbial composition by uptake of probiotic-rich food can act as a preventive/therapeutic option for AD. The objective of the present review is to summarize the recent findings on the role of gut microbiota in the development of AD. Understanding the relationship between gut microbiota and CNS will help identify novel therapeutic strategies, especially probiotic-based supplementation, for the treatment of AD.


Asunto(s)
Enfermedad de Alzheimer/microbiología , Enfermedad de Alzheimer/fisiopatología , Encéfalo/fisiopatología , Microbioma Gastrointestinal , Probióticos/uso terapéutico , Envejecimiento , Enfermedad de Alzheimer/tratamiento farmacológico , Amiloide/química , Precursor de Proteína beta-Amiloide/genética , Animales , Barrera Hematoencefálica , Sistema Nervioso Central , Humanos , Mucosa Intestinal/patología , Lipopolisacáridos/química , Ratones , Ratones Transgénicos , Permeabilidad , Ratas
17.
Anesth Analg ; 132(1): 108-109, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33315608
18.
Clin Nucl Med ; 46(2): e75-e77, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33234934

RESUMEN

ABSTRACT: We report an increased uptake of 18F-choline in the right cerebellopontine angle area in a 73-year-old man with biochemical failure prostate cancer after radical prostatectomy, potentially suggestive of bone metastasis in the base of the skull. A brain MRI was also performed showing an intense gadolinium enhancement focus in the same area, concordant with a right vestibular schwannoma, subsequently histologically proven. This case underlines that schwannoma is a diagnostic pitfall in 18F-choline PET/CT, suggesting this radiolabeled tracer as a promising tool for brain tumors characterization due to its higher signal-to-background ratio than 18F-FDG.


Asunto(s)
Colina/análogos & derivados , Hallazgos Incidentales , Neuroma Acústico/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Anciano , Neoplasias Óseas/secundario , Encéfalo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroma Acústico/secundario , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Insuficiencia del Tratamiento
19.
Neurosci Lett ; 742: 135528, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-33248159

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) for which there have been over 50 million confirmed cases and 1.2 million deaths globally. While many SARS-CoV-2 infected individuals are asymptomatic or experience respiratory symptoms, extrapulmonary manifestations, including neurological symptoms and conditions, are increasingly recognized. There remains no clear understanding of the mechanisms that underlie neurological symptoms in COVID-19 and whether SARS-CoV-2 has the potential for neuroinvasion in humans. In this minireview, we discuss what is known from human autopsies in fatal COVID-19, including highlighting studies that investigate for the presence of SARS-CoV-2 in brain and olfactory tissue, and summarize the neuropathological consequences of infection. Incorporating microscopic and molecular findings from brain tissue into what we know about clinical disease will inform best practice management guidance and direct research priorities as it relates to neurological morbidity from COVID-19.


Asunto(s)
Encéfalo/patología , Encéfalo/virología , /aislamiento & purificación , Autopsia , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos
20.
Neurosci Lett ; 742: 135533, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-33248163

RESUMEN

COVID-19 has shaken the core of the medical health system. The wide spread death and destruction of patients and health care workers in unprecedented in the modern era. While the pulmonary complications have received the most attention, it is the neurological manifestations that are disabling, persistent and common in patients infected with SARS-CoV-2. The entire neuro-axis can be involved resulting in a wide variety of manifestations. While the pathophysiology is not well understood, many of the clinical manifestations seem to be immune mediated. The socio-economic consequences of these complications are dire. These unprecedented times also calls for unprecedented action. Novel clinical trial designs need to be considered so that multiple agents can be studied. In the context of these clinical trials, disease pathophysiology and standardized batteries and biological markers for patient assessment need to be developed.


Asunto(s)
Encéfalo/patología , /patología , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/patología , /metabolismo , Humanos , Enfermedades del Sistema Nervioso/metabolismo
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