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1.
Microcirculation ; 31(3): e12845, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38265175

RESUMO

OBJECTIVE: The role of cerebral microvasculature in cognitive dysfunction can be investigated by identifying the impact of blood flow on cortical tissue oxygenation. In this paper, the impact of capillary stalls on microcirculatory characteristics such as flow and hematocrit (Ht) in the cortical angioarchitecture is studied. METHODS: Using a deterministic mathematical model to simulate blood flow in a realistic mouse cortex, hemodynamics parameters, including pressure, flow, vessel diameter-adjustable hematocrit, and transit time are calculated as a function of stalling events. RESULTS: Using a non-linear plasma skimming model, it is observed that Ht increases in the penetrating arteries from the pial vessels as a function of cortical depth. The incidence of stalling on Ht distribution along the blood network vessels shows reduction of RBCs around the tissue near occlusion sites and decreased Ht concentration downstream from the blockage points. Moreover, upstream of the occlusion, there is a noticeable increase of the Ht, leading to larger flow resistance due to higher blood viscosity. We predicted marked changes in transit time behavior due to stalls which match trends observed in mice in vivo. CONCLUSIONS: These changes to blood cell quantity and quality may be implicated in the development of Alzheimer's disease and contribute to the course of the illness.


Assuntos
Eritrócitos , Hemodinâmica , Camundongos , Animais , Microcirculação/fisiologia , Hemodinâmica/fisiologia , Hematócrito , Eritrócitos/fisiologia , Encéfalo
2.
Can J Neurol Sci ; 50(1): 72-82, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850674

RESUMO

OBJECTIVE: Uncontrolled epilepsy creates a constant source of worry for patients and puts them at a high risk of injury. Identifying recurrent "premonitory" symptoms of seizures and using them to recalibrate seizure prediction algorithms may improve prediction performances. This study aimed to investigate patients' ability to predict oncoming seizures based on preictal symptoms. METHODS: Through an online survey, demographics and clinical characteristics (e.g., seizure frequency, epilepsy duration, and postictal symptom duration) were collected from people with epilepsy and caregivers across Canada. Respondents were asked to answer questions regarding their ability to predict seizures through warning symptoms. A total of 196 patients and 150 caregivers were included and were separated into three groups: those who reported warning symptoms within the 5 minutes preceding a seizure, prodromes (symptoms earlier than 5 minutes before seizure), and no warning symptoms. RESULTS: Overall, 12.2% of patients and 12.0% of caregivers reported predictive prodromes ranging from 5 minutes to more than 24 hours before the seizures (median of 2 hours). The most common were dizziness/vertigo (28%), mood changes (26%), and cognitive changes (21%). Statistical testing showed that respondents who reported prodromes also reported significantly longer postictal recovery periods compared to those who did not report predictive prodromes (P < 0.05). CONCLUSION: Findings suggest that patients who present predictive seizure prodromes may be characterized by longer patient-reported postictal recovery periods. Studying the correlation between seizure severity and predictability and investigating the electrical activity underlying prodromes may improve our understanding of preictal mechanisms and ability to predict seizures.


Assuntos
Cuidadores , Epilepsia , Humanos , Epilepsia/diagnóstico , Convulsões , Inquéritos e Questionários , Algoritmos , Eletroencefalografia
3.
PLoS Comput Biol ; 17(1): e1008584, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507970

RESUMO

Departures of normal blood flow and metabolite distribution from the cerebral microvasculature into neuronal tissue have been implicated with age-related neurodegeneration. Mathematical models informed by spatially and temporally distributed neuroimage data are becoming instrumental for reconstructing a coherent picture of normal and pathological oxygen delivery throughout the brain. Unfortunately, current mathematical models of cerebral blood flow and oxygen exchange become excessively large in size. They further suffer from boundary effects due to incomplete or physiologically inaccurate computational domains, numerical instabilities due to enormous length scale differences, and convergence problems associated with condition number deterioration at fine mesh resolutions. Our proposed simple finite volume discretization scheme for blood and oxygen microperfusion simulations does not require expensive mesh generation leading to the critical benefit that it drastically reduces matrix size and bandwidth of the coupled oxygen transfer problem. The compact problem formulation yields rapid and stable convergence. Moreover, boundary effects can effectively be suppressed by generating very large replica of the cortical microcirculation in silico using an image-based cerebrovascular network synthesis algorithm, so that boundaries of the perfusion simulations are far removed from the regions of interest. Massive simulations over sizeable portions of the cortex with feature resolution down to the micron scale become tractable with even modest computer resources. The feasibility and accuracy of the novel method is demonstrated and validated with in vivo oxygen perfusion data in cohorts of young and aged mice. Our oxygen exchange simulations quantify steep gradients near penetrating blood vessels and point towards pathological changes that might cause neurodegeneration in aged brains. This research aims to explain mechanistic interactions between anatomical structures and how they might change in diseases or with age. Rigorous quantification of age-related changes is of significant interest because it might aide in the search for imaging biomarkers for dementia and Alzheimer's disease.


Assuntos
Envelhecimento/fisiologia , Córtex Cerebral , Hipóxia/metabolismo , Modelos Cardiovasculares , Oxigênio/metabolismo , Algoritmos , Animais , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Biologia Computacional/métodos , Simulação por Computador , Hipóxia/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Camundongos , Microcirculação/fisiologia , Microscopia Confocal
4.
BMC Geriatr ; 22(1): 648, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941561

RESUMO

BACKGROUND: Aging is associated with an increased likelihood of developing dementia, but a growing body of evidence suggests that certain modifiable risk factors may help prevent or delay dementia onset. Among these, physical activity (PA) has been linked to better cognitive performance and brain functions in healthy older adults and may contribute to preventing dementia. The current pilot study investigated changes in behavioral and brain activation patterns over a 1-year period in individuals with mild cognitive impairment (MCI) and healthy controls taking part in regular PA. METHODS: Frontal cortical response during a dual-task walking paradigm was investigated at baseline, at 6 months (T6), and at 12 months (T12) by means of a portable functional Near-Infrared Spectroscopy (fNIRS) system. The dual-task paradigm included a single cognitive task (2-back), a single motor task (walking), and a dual-task condition (2-back whilst walking). RESULTS: Both groups showed progressive improvement in cognitive performance at follow-up visits compared to baseline. Gait speed remained stable throughout the duration of the study in the control group and increased at T6 for those with MCI. A significant decrease in cortical activity was observed in both groups during the cognitive component of the dual-task at follow-up visits compared to baseline, with MCI individuals showing the greatest improvement. CONCLUSIONS: The observations of this pilot study suggest that taking part in regular PA may be especially beneficial for both cognitive performance and brain functions in older adulthood and, especially, in individuals with MCI. Our findings may serve as preliminary evidence for the use of PA as a potential intervention to prevent cognitive decline in individuals at greater risk of dementia.


Assuntos
Disfunção Cognitiva , Demência , Idoso , Encéfalo , Cognição , Demência/complicações , Marcha/fisiologia , Humanos , Projetos Piloto
5.
Hum Brain Mapp ; 42(12): 3760-3776, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-33991155

RESUMO

Recent studies have reported that optical indices of cerebral pulsatility are associated with cerebrovascular health in older adults. Such indices, including cerebral pulse amplitude and the pulse relaxation function (PRF), have been previously applied to quantify global and regional cerebral pulsatility. The aim of the present study was to determine whether these indices are modulated by cardiovascular status and whether they differ between individuals with low or high cardiovascular risk factors (LCVRF and HCVRF) and coronary artery disease (CAD). A total of 60 older adults aged 57-79 were enrolled in the study. Participants were grouped as LCVRF, HCVRF, and CAD. Participants were asked to walk freely on a gym track while a near-infrared spectroscopy (NIRS) device recorded hemodynamics data. Low-intensity, short-duration walking was used to test whether a brief cardiovascular challenge could increase the difference of pulsatility indices with respect to cardiovascular status. Results indicated that CAD individuals have higher global cerebral pulse amplitude compared with the other groups. Walking reduced global cerebral pulse amplitude and PRF in all groups but did not increase the difference across the groups. Instead, walking extended the spatial distribution of cerebral pulse amplitude to the anterior prefrontal cortex when CAD was compared to the CVRF groups. Further research is needed to determine whether cerebral pulse amplitude extracted from data acquired with NIRS, which is a noninvasive, inexpensive method, can provide an index to characterize the cerebrovascular status associated with CAD.


Assuntos
Circulação Cerebrovascular/fisiologia , Cérebro/fisiopatologia , Doença da Artéria Coronariana/fisiopatologia , Neuroimagem Funcional , Pulso Arterial , Espectroscopia de Luz Próxima ao Infravermelho , Idoso , Cérebro/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Am J Physiol Heart Circ Physiol ; 316(6): H1281-H1296, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901279

RESUMO

MK5 is a protein serine/threonine kinase activated by p38, ERK3, and ERK4 MAPKs. MK5 mRNA and immunoreactivity are detected in mouse cardiac fibroblasts, and MK5 haplodeficiency attenuates the increase in collagen 1-α1 mRNA evoked by pressure overload. The present study examined the effect of MK5 haplodeficiency on reparative fibrosis following myocardial infarction (MI). Twelve-week-old MK5+/- and wild-type littermate (MK5+/+) mice underwent ligation of the left anterior descending coronary artery (LADL). Surviving mice were euthanized 8 or 21 days post-MI. Survival rates did not differ significantly between MK5+/+ and MK5+/- mice, with rupture of the LV wall being the primary cause of death. Echocardiographic imaging revealed similar increases in LV end-diastolic diameter, myocardial performance index, and wall motion score index in LADL-MK5+/+ and LADL-MK5+/- mice. Area at risk did not differ between LADL-MK5+/+ and LADL-MK5+/- hearts. In contrast, infarct size, scar area, and scar collagen content were reduced in LADL-MK5+/- hearts. Immunohistochemical analysis of mice experiencing heart rupture revealed increased MMP-9 immunoreactivity in the infarct border zone of LADL-MK5+/- hearts compared with LADL-MK5+/+. Although inflammatory cell infiltration was similar in LADL-MK5+/+ and LADL-MK5+/- hearts, angiogenesis was more pronounced in the infarct border zone of LADL-MK5+/- mice. Characterization of ventricular fibroblasts revealed reduced motility and proliferation in fibroblasts isolated from MK5-/- mice compared with those from both wild-type and haplodeficient mice. siRNA-mediated knockdown of MK5 in fibroblasts from wild-type mice also impaired motility. Hence, reduced MK5 expression alters fibroblast function and scar morphology but not mortality post-MI. NEW & NOTEWORTHY MK5/PRAK is a protein serine/threonine kinase activated by p38 MAPK and/or atypical MAPKs ERK3/4. MK5 haplodeficiency reduced infarct size, scar area, and scar collagen content post-myocardial infarction. Motility and proliferation were reduced in cultured MK5-null cardiac myofibroblasts.


Assuntos
Cicatriz/enzimologia , Colágeno/metabolismo , Haploinsuficiência , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Infarto do Miocárdio/enzimologia , Miocárdio/enzimologia , Miofibroblastos/enzimologia , Proteínas Serina-Treonina Quinases/deficiência , Cicatrização , Animais , Movimento Celular , Proliferação de Células , Células Cultivadas , Cicatriz/patologia , Cicatriz/fisiopatologia , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Miofibroblastos/patologia , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Função Ventricular Esquerda , Remodelação Ventricular
7.
Brain Behav Immun ; 81: 348-360, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31247289

RESUMO

Perinatal infection and inflammatory episodes in preterm infants are associated with diffuse white matter injury (WMI) and adverse neurological outcomes. Inflammation-induced WMI was previously shown to be linked with later hippocampal atrophy as well as learning and memory impairments in preterm infants. Early evaluation of injury load and therapeutic response with non-invasive tools such as multimodal magnetic resonance imaging (MRI) would greatly improve the search of new therapeutic approaches in preterm infants. Our aim was to evaluate the potential of multimodal MRI to detect the response of interleukin-1 receptor antagonist (IL-1Ra) treatment, known for its neuroprotective properties, during the acute phase of injury on a model of neonatal WMI. Rat pups at postnatal day 3 (P3) received intracerebral injection of lipopolysaccharide with systemic IL-1Ra therapy. 24 h later (P4), rats were imaged with multimodal MRI to assess microstructure by diffusion tensor imaging (DTI) and neurochemical profile of the hippocampus with 1H-magnetic resonance spectroscopy. Astrocyte and microglial activation, apoptosis and the mRNA expression of pro-inflammatory and necroptotic markers were assessed. During the acute phase of injury, neonatal LPS exposure altered the concentration of hippocampus metabolites related to neuronal integrity, neurotransmission and membrane integrity and induced diffusivity restriction. Just 24 h after initiation of therapy, early indication of IL-1Ra neuroprotective effect could be detected in vivo by non-invasive spectroscopy and DTI, and confirmed with immunohistochemical evaluation and mRNA expression of inflammatory markers and cell death. In conclusion, multimodal MRI, particularly DTI, can detect not only injury but also the acute therapeutic effect of IL-1Ra suggesting that MRI could be a useful non-invasive tool to follow, at early time points, the therapeutic response in preterm infants.


Assuntos
Imagem Multimodal/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Hipocampo/efeitos dos fármacos , Inflamação/complicações , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/farmacologia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Fármacos Neuroprotetores/farmacologia , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-1/antagonistas & inibidores , Receptores de Interleucina-1/metabolismo
8.
Hum Brain Mapp ; 39(1): 7-23, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29058341

RESUMO

Continuous brain imaging techniques can be beneficial for the monitoring of neurological pathologies (such as epilepsy or stroke) and neuroimaging protocols involving movement. Among existing ones, functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) have the advantage of being noninvasive, nonobstructive, inexpensive, yield portable solutions, and offer complementary monitoring of electrical and local hemodynamic activities. This article presents a novel system with 128 fNIRS channels and 32 EEG channels with the potential to cover a larger fraction of the adult superficial cortex than earlier works, is integrated with 32 EEG channels, is light and battery-powered to improve portability, and can transmit data wirelessly to an interface for real-time display of electrical and hemodynamic activities. A novel fNIRS-EEG stretchable cap, two analog channels for auxiliary data (e.g., electrocardiogram), eight digital triggers for event-related protocols and an internal accelerometer for movement artifacts removal contribute to improve data acquisition quality. The system can run continuously for 24 h. Following instrumentation validation and reliability on a solid phantom, performance was evaluated on (1) 12 healthy participants during either a visual (checkerboard) task at rest or while pedalling on a stationary bicycle or a cognitive (language) task and (2) 4 patients admitted either to the epilepsy (n = 3) or stroke (n = 1) units. Data analysis confirmed expected hemodynamic variations during validation recordings and useful clinical information during in-hospital testing. To the best of our knowledge, this is the first demonstration of a wearable wireless multichannel fNIRS-EEG monitoring system in patients with neurological conditions. Hum Brain Mapp 39:7-23, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Eletroencefalografia/instrumentação , Monitorização Neurofisiológica/instrumentação , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Dispositivos Eletrônicos Vestíveis , Tecnologia sem Fio , Adolescente , Adulto , Ciclismo/fisiologia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/fisiologia , Córtex Cerebral/fisiopatologia , Circulação Cerebrovascular , Cognição/fisiologia , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Feminino , Neuroimagem Funcional/instrumentação , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Percepção Visual/fisiologia , Adulto Jovem
9.
Biomacromolecules ; 19(1): 112-131, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29211954

RESUMO

Chitosan (CS) shows in vitro and in vivo efficacy for siRNA delivery but with contradictory findings for incompletely characterized systems. For understanding which parameters produce effective delivery, a library of precisely characterized chitosans was produced at different degrees of deacetylation (DDAs) and average molecular weights (Mn). Encapsulation and transfection efficiencies were characterized in vitro. Formulations were selected to examine the influence of Mn and N:P ratio on nanoparticle uptake, metabolic activity, genotoxicity, and in vitro transfection. Hemocompatibility and in vivo biodistribution were then investigated for different Mn, N:P ratios, and doses. Nanoparticle uptake and gene silencing correlated with increased surface charge, which was obtained at high DDA and high Mn. A minimum polymer length of ∼60-70 monomers (∼10 kDa) was required for stability and knockdown. In vitro knockdown was equivalent to lipid control with no metabolic or genotoxicity. An inhibitory effect of serum on biological performance was dependent on DDA, Mn, and N:P. In vivo biodistribution in mice show accumulation of nanoparticles in kidney with 40-50% functional knockdown.


Assuntos
Aminas/metabolismo , Materiais Biocompatíveis/química , Quitosana/administração & dosagem , Inativação Gênica , Nanopartículas/química , Fosfatos/metabolismo , RNA Interferente Pequeno/administração & dosagem , Acetilação , Sangue , Linhagem Celular Tumoral , Quitosana/química , Quitosana/farmacocinética , Ensaio Cometa , Células Epiteliais/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Peso Molecular , Nanopartículas/toxicidade , Reação em Cadeia da Polimerase em Tempo Real , Distribuição Tecidual
10.
Molecules ; 23(11)2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30400168

RESUMO

Gold nanostructures that can be synthetically articulated to adapt diverse morphologies, offer a versatile platform and tunable properties for applications in a variety of areas, including biomedicine and diagnostics. Among several conformational architectures, gold nanoshells provide a highly advantageous combination of properties that can be fine-tuned in designing single or multi-purpose nanomaterials, especially for applications in biology. One of the important parameters for evaluating the efficacy of gold nano-architectures is their reproducible synthesis and surface functionalization with desired moieties. A variety of methods now exist that allow fabrication and chemical manipulation of their structure and resulting properties. This review article provides an overview and a discussion of synthetic methodologies to a diverse range of gold nanoshells, and a brief summary of surface functionalization and characterization methods employed to evaluate their overall composition.


Assuntos
Técnicas de Química Sintética , Ouro/química , Nanoconchas/química , Fenômenos Químicos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Nanoconchas/ultraestrutura , Tamanho da Partícula , Análise Espectral , Ressonância de Plasmônio de Superfície
11.
Neuroimage ; 149: 436-445, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28043909

RESUMO

Magnetic resonance fingerprinting (MRF) was recently proposed as a novel strategy for MR data acquisition and analysis. A variant of MRF called vascular MRF (vMRF) followed, that extracted maps of three parameters of physiological importance: cerebral oxygen saturation (SatO2), mean vessel radius and cerebral blood volume (CBV). However, this estimation was based on idealized 2-dimensional simulations of vascular networks using random cylinders and the empirical Bloch equations convolved with a diffusion kernel. Here we focus on studying the vascular MR fingerprint using real mouse angiograms and physiological values as the substrate for the MR simulations. The MR signal is calculated ab initio with a Monte Carlo approximation, by tracking the accumulated phase from a large number of protons diffusing within the angiogram. We first study the identifiability of parameters in simulations, showing that parameters are fully estimable at realistically high signal-to-noise ratios (SNR) when the same angiogram is used for dictionary generation and parameter estimation, but that large biases in the estimates persist when the angiograms are different. Despite these biases, simulations show that differences in parameters remain estimable. We then applied this methodology to data acquired using the GESFIDE sequence with SPIONs injected into 9 young wild type and 9 old atherosclerotic mice. Both the pre injection signal and the ratio of post-to-pre injection signals were modeled, using 5-dimensional dictionaries. The vMRF methodology extracted significant differences in SatO2, mean vessel radius and CBV between the two groups, consistent across brain regions and dictionaries. Further validation work is essential before vMRF can gain wider application.


Assuntos
Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Animais , Aterosclerose/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Angiografia Cerebral , Camundongos , Camundongos Endogâmicos C57BL
12.
J Neurosci ; 35(8): 3663-75, 2015 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-25716864

RESUMO

The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences.


Assuntos
Encéfalo/irrigação sanguínea , Interpretação de Imagem Assistida por Computador/métodos , Angiografia por Ressonância Magnética/métodos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Modelos Cardiovasculares , Animais , Encéfalo/fisiologia , Corantes Fluorescentes , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Consumo de Oxigênio , Ratos , Ratos Sprague-Dawley
13.
Neuroimage ; 126: 239-55, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26619785

RESUMO

Functional near-infrared spectroscopy (fNIRS) can be combined with electroencephalography (EEG) to continuously monitor the hemodynamic signal evoked by epileptic events such as seizures or interictal epileptiform discharges (IEDs, aka spikes). As estimation methods assuming a canonical shape of the hemodynamic response function (HRF) might not be optimal, we sought to model patient-specific HRF (sHRF) with a simple deconvolution approach for IED-related analysis with EEG-fNIRS data. Furthermore, a quadratic term was added to the model to account for the nonlinearity in the response when IEDs are frequent. Prior to analyzing clinical data, simulations were carried out to show that the HRF was estimable by the proposed deconvolution methods under proper conditions. EEG-fNIRS data of five patients with refractory focal epilepsy were selected due to the presence of frequent clear IEDs and their unambiguous focus localization. For each patient, both the linear sHRF and the nonlinear sHRF were estimated at each channel. Variability of the estimated sHRFs was seen across brain regions and different patients. Compared with the SPM8 canonical HRF (cHRF), including these sHRFs in the general linear model (GLM) analysis led to hemoglobin activations with higher statistical scores as well as larger spatial extents on all five patients. In particular, for patients with frequent IEDs, nonlinear sHRFs were seen to provide higher sensitivity in activation detection than linear sHRFs. These observations support using sHRFs in the analysis of IEDs with EEG-fNIRS data.


Assuntos
Córtex Cerebral/fisiopatologia , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Modelos Neurológicos , Acoplamento Neurovascular/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
14.
Hum Brain Mapp ; 37(9): 3250-61, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27220112

RESUMO

Failure to recognize insular cortex seizures has recently been identified as a cause of epilepsy surgeries targeting the temporal, parietal, or frontal lobe. Such failures are partly due to the fact that current noninvasive localization techniques fare poorly in recognizing insular epileptic foci. Our group recently demonstrated that magnetoencephalography (MEG) is sensitive to epileptiform spikes generated by the insula. In this study, we assessed the potential of distributed source imaging and functional connectivity analyses to distinguish insular networks underlying the generation of spikes. Nineteen patients with operculo-insular epilepsy were investigated. Each patient underwent MEG as well as T1-weighted magnetic resonance imaging (MRI) as part of their standard presurgical evaluation. Cortical sources of MEG spikes were reconstructed with the maximum entropy on the mean algorithm, and their time courses served to analyze source functional connectivity. The results indicate that the anterior and posterior subregions of the insula have specific patterns of functional connectivity mainly involving frontal and parietal regions, respectively. In addition, while their connectivity patterns are qualitatively similar during rest and during spikes, couplings within these networks are much stronger during spikes. These results show that MEG can establish functional connectivity-based signatures that could help in the diagnosis of different subtypes of insular cortex epilepsy. Hum Brain Mapp 37:3250-3261, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Córtex Cerebral/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Vias Neurais/fisiopatologia , Adolescente , Mapeamento Encefálico , Criança , Epilepsia/cirurgia , Feminino , História do Século XVI , Humanos , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Exp Eye Res ; 146: 330-340, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27060375

RESUMO

Oximetry measurement of principal retinal vessels represents a first step towards understanding retinal metabolism, but the technique could be significantly enhanced by spectral imaging of the fundus outside of main vessels. In this study, a recently developed Hyperspectral Retinal Camera was used to measure relative oximetric (SatO2) and total hemoglobin (HbT) maps of the retina, outside of large vessels, in healthy volunteers at baseline (N = 7) and during systemic hypoxia (N = 11), as well as in patients with glaucoma (N = 2). Images of the retina, on a field of view of ∼30°, were acquired between 500 and 600 nm with 2 and 5 nm steps, in under 3 s. The reflectance spectrum from each pixel was fitted to a model having oxy- and deoxyhemoglobin as the main absorbers and scattering modeled by a power law, yielding estimates of relative SatO2 and HbT over the fundus. Average optic nerve head (ONH) saturation over 8 eyes was 68 ± 5%. During systemic hypoxia, mean ONH saturation decreased by 12.5% on average. Upon further development and validation, the relative SatO2 and HbT maps of microvasculature obtained with this imaging system could ultimately contribute to the diagnostic and management of diseases affecting the ONH and retina.


Assuntos
Disco Óptico/fisiologia , Oximetria/métodos , Oxigênio/metabolismo , Vasos Retinianos/fisiologia , Adulto , Glaucoma/metabolismo , Hemoglobinas/metabolismo , Humanos , Hipóxia/metabolismo , Modelos Lineares , Fluxo Sanguíneo Regional/fisiologia , Adulto Jovem
16.
Nanotechnology ; 27(41): 415602, 2016 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-27608753

RESUMO

We report the design of scaffolds containing mono-, bis-, and tris-phosphonate coordinating groups, and a polyethylene glycol chain, for stabilizing superparamagnetic iron oxide nanoparticles (SPIONs), using simple and versatile chemistry. We demonstrate that the number of anchoring phosphonate sites on the ligand influence the colloidal stability, magnetic and biological properties of SPIONs, and the latter do not solely depend on attaching moieties that can enhance their aqueous dispersion. These parameters can be tailored by the number of conjugation sites on the ligand, as evidenced from dynamic light scattering at various salt concentrations, magnetic relaxivities and cell viability studies.

17.
Proc Natl Acad Sci U S A ; 110(24): 9974-9, 2013 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-23716671

RESUMO

Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-d-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation.


Assuntos
Moléculas de Adesão Celular Neuronais/fisiologia , Neurônios/fisiologia , Sono/fisiologia , Vigília/fisiologia , Animais , Western Blotting , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Eletroencefalografia , Eletromiografia , Expressão Gênica , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos AKR , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Neurônios/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sono/genética , Privação do Sono/genética , Privação do Sono/fisiopatologia , Especificidade da Espécie , Fatores de Tempo , Vigília/genética
18.
Int J Mol Sci ; 17(12)2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27983695

RESUMO

Atherosclerotic cardiovascular diseases are characterized by the formation of a plaque in the arterial wall. Intravascular ultrasound (IVUS) provides high-resolution images allowing delineation of atherosclerotic plaques. When combined with near infrared fluorescence (NIRF), the plaque can also be studied at a molecular level with a large variety of biomarkers. In this work, we present a system enabling automated volumetric histology imaging of excised aortas that can spatially correlate results with combined IVUS/NIRF imaging of lipid-rich atheroma in cholesterol-fed rabbits. Pullbacks in the rabbit aortas were performed with a dual modality IVUS/NIRF catheter developed by our group. Ex vivo three-dimensional (3D) histology was performed combining optical coherence tomography (OCT) and confocal fluorescence microscopy, providing high-resolution anatomical and molecular information, respectively, to validate in vivo findings. The microscope was combined with a serial slicer allowing for the imaging of the whole vessel automatically. Colocalization of in vivo and ex vivo results is demonstrated. Slices can then be recovered to be tested in conventional histology.


Assuntos
Vasos Sanguíneos/patologia , Imageamento Tridimensional , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Tomografia de Coerência Óptica/métodos , Animais , Anticorpos/metabolismo , Artefatos , Catéteres , Molécula 1 de Adesão Intercelular/imunologia , Masculino , Coelhos
19.
Brain Cogn ; 98: 1-14, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26046834

RESUMO

Age-related differences in the ability to perform two tasks simultaneously (or dual-task) have become a major concern in aging neurosciences and have often been assessed with two distinct paradigms; the Psychological Refractory Period (PRP) and the Dual-Task (DT) paradigms. PRP studies assess participants when they give Priority to one task over the other (complete A then B), whereas in DT studies participants give Equal priority to both tasks (complete A and B). The Equal condition could be viewed as adding an executive control component to the task since the participants must spontaneously monitor attention between tasks. In the current study, we assessed the effect of priority instructions (Priority vs. Equal) on the dual-task performance and brain activity of younger (n = 16) and older adults (n = 19) with functional near infra-red spectroscopy (fNIRS). In younger adults, the Priority condition showed right-sided activation in the prefrontal cortex during DT execution. Older adults showed bilateral frontal activation, yet restrained to specific areas. They showed increased activation in DT vs. single task condition in the left dorsolateral prefrontal cortex (DLPFC) and the bilateral ventrolateral prefrontal cortex (VLPFC). In the Equal condition, the DT condition showed isolated left DLPFC and VLPFC activation in younger adults and widespread bilateral DLPFC activation in older adults. These results suggest that for both older and younger adults, priority effects are associated with distinct patterns of prefrontal activation. Age-related differences also exist in these patterns such that prefrontal activation seems to be more spread out at different sites in older adults when they are instructed to give Equal priority to both tasks.


Assuntos
Envelhecimento/fisiologia , Função Executiva/fisiologia , Neuroimagem Funcional/métodos , Córtex Pré-Frontal/fisiologia , Desempenho Psicomotor/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Eur J Appl Physiol ; 115(10): 2189-97, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26063061

RESUMO

PURPOSE: To assess the relationship between exercise intensity, cerebral HbO2 and cognitive performance (Executive and non-Executive) in young adults. METHODS: We measured reaction time (RT) and accuracy, during a computerized Stroop task, in 19 young adults (7 males and 12 females). Their mean ± SD age, height, body mass and body mass index (BMI) were 24 ± 4 years, 1.67 ± 0.07 m, 72 ± 14 kg and 25 ± 3 kg m(-2), respectively. Each subject performed the Stroop task at rest and during cycling at exercise of low intensity [40% of peak power output (PPO)], moderate intensity (60% of PPO) and high intensity (85% of PPO). Cerebral oxygenation was monitored during the resting and exercise conditions over the prefrontal cortex (PFC) using near-infrared spectroscopy (NIRS). RESULTS: High-intensity exercise slowed RT in both the Naming (p = 0.04) and the Executive condition (p = 0.04). The analysis also revealed that high-intensity exercise was associated with a decreased accuracy when compared to low-intensity exercise (p = 0.021). Neuroimaging results confirm a decrease of cerebral oxygenation during high-intensity exercise in comparison to low- (p = 0.004) and moderate-intensity exercise (p = 0.003). Correlations revealed that a lower cerebral HbO2 in the prefrontal cortex was associated with slower RT in the Executive condition only (p = 0.04, g = -0.72). CONCLUSION: Results of the present study suggest that low to moderate exercise intensity does not alter Executive functioning, but that exercise impairs cognitive functions (Executive and non-Executive) when the physical workload becomes heavy. The cerebral HbO2 correlation suggests that a lower availability of HbO2 was associated with slower RT in the Executive condition only.


Assuntos
Encéfalo/fisiologia , Circulação Cerebrovascular , Cognição , Exercício Físico , Consumo de Oxigênio , Adulto , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino
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