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1.
Eur Radiol ; 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37955671

RESUMO

OBJECTIVES: The purpose of this study was to evaluate a three-material decomposition algorithm for hepatic fat quantification using a dual-layer computed tomography (DL-CT) and MRI as reference standard on a large patient cohort. METHOD: A total of 104 patients were retrospectively included in our study, i.e., each patient had an MRI exam and a DL-CT exam in our institution within a maximum of 31 days. Four regions of interest (ROIs) were positioned blindly and similarly in the liver, by two independent readers on DL-CT and MRI images. For DL-CT exams, all imaging phases were included. Fat fraction agreement between CT and MRI was performed using intraclass correlation coefficients (ICC), determination coefficients R2, and Bland-Altman plots. Diagnostic performance was determined using sensitivity, specificity, and positive and negative predictive values. The cutoff for steatosis was 5%. RESULTS: Correlation between MRI and CT data was excellent for all perfusion phases with ICC calculated at 0.99 for each phase. Determination coefficients R2 were also good for all perfusion phases (about 0.95 for all phases). Performance of DL-CT in the diagnosis of hepatic steatosis was good with sensitivity between 89 and 91% and specificity ranging from 75 to 80%, depending on the perfusion phase. The positive predictive value was ranging from 78 to 93% and the negative predictive value from 82 to 86%. CONCLUSION: Multi-material decomposition in DL-CT allows quantification of hepatic fat fraction with a good correlation to MRI data. CLINICAL RELEVANCE STATEMENT: The use of DL-CT allows for detection of hepatic steatosis. This is especially interesting as an opportunistic finding CT performed for other reasons, as early detection can help prevent or slowdown the development of liver metabolic disease. KEY POINTS: • Hepatic fat fractions provided by the dual-layer CT algorithm is strongly correlated with that measured on MRI. • Dual-layer CT is accurate to detect hepatic steatosis ≥ 5%. • Dual-layer CT allows opportunistic detection of steatosis, on CT scan performed for various indications.

2.
Eur J Neurosci ; 50(12): 3985-4003, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31325398

RESUMO

A complex scenario of cellular network reorganization is caused by unilateral sensory deafferentation (USD) in the adult rat central auditory system. We asked whether this plasticity response involves mitosis. Immunohistochemistry was applied to brainstem sections for the detection and localization of mitotic markers Ki67 and PCNA, the growth-associated protein Gap43 and purine receptor P2X4. Fluorescent double staining was done for Ki67:PCNA and for both of them with HuC/HuD (neurons), S100 (astrocytes), Iba1 (microglia) and P2X4. Inquiring 1-7 days after USD, we found Ki67 expression to be changed in cellular profiles of cochlear nucleus (CN) with a significant increase in number by 1-3 days, followed by reset to control level within 1 week. USD-induced mitosis exclusively occurred in microglia and was absent elsewhere in the auditory brainstem. PCNA staining of small cellular profiles increased similarly but remained elevated. PCNA staining intensity also changed in CN, superior olive and inferior colliculus in neuronal nuclei, suggesting shifts in DNA processing. No apoptotic cell death was detected in any region of the adult auditory brainstem after USD. A comparison of anterograde and retrograde effects of nerve damage revealed proliferating microglia expressing P2X4 receptors in CN upon USD, but not in the facial nucleus after facial nerve transection. In conclusion, the deafferentation model studied here permits insight into the capacity of the adult mammalian brain to invoke mitosis among glia cells, adjustment of gene processing in neurons and purinergic signalling between them, jointly accounting for a multilayered neuro- and glioplastic response.


Assuntos
Astrócitos/metabolismo , Tronco Encefálico/metabolismo , DNA/metabolismo , Neurônios/metabolismo , Animais , Vias Auditivas/metabolismo , Núcleo Coclear/metabolismo , Colículos Inferiores/metabolismo , Microglia/metabolismo , Ratos
3.
Magn Reson Med ; 77(2): 581-591, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-26959278

RESUMO

PURPOSE: Inhomogeneous magnetization transfer (ihMT) shows great promise for specific imaging of myelinated tissues. Whereas the ihMT technique has been previously applied in brain applications, the current report presents a strategy for cervical spinal cord (SC) imaging free of cerebrospinal fluid (CSF) pulsatility artifacts. METHODS: A pulsed ihMT preparation was combined with a single-shot HASTE readout. Electrocardiogram (ECG) synchronization was used to acquire all images during the quiescent phase of SC motion. However ihMT signal quantification errors may occur when a variable recovery delay is introduced in the sequence as a consequence of variable cardiac cycle. A semiautomatic retrospective correction algorithm, based on repetition time (TR) -matching, is proposed to correct for signal variations of long T1 -components (e.g., CSF). RESULTS: The proposed strategy combining ECG synchronization and retrospective data pairing led to clean SC images free of CSF artifacts. Lower variability of the ihMT metrics were obtained with the correction algorithm, and allowed for shorter TR to be used, hence improving signal-to-noise ratio efficiency. CONCLUSION: The proposed methodology enabled faster acquisitions, while offering robust ihMT quantification and exquisite SC image quality. This opens great perspectives for widening the in vivo characterization of SC physiopathology using MRI, such as studying white matter tracts microstructure or impairment in degenerative pathologies. Magn Reson Med 77:581-591, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Assuntos
Algoritmos , Artefatos , Técnicas de Imagem de Sincronização Cardíaca/métodos , Líquido Cefalorraquidiano/citologia , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Medula Espinal/anatomia & histologia , Adulto , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Movimento (Física) , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
4.
Magn Reson Med ; 76(1): 70-82, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26301785

RESUMO

PURPOSE: In this study, we proposed an efficient free-breathing strategy for rapid and improved cardiac diffusion-weighted imaging (DWI) acquisition using a single-shot spin-echo echo planar imaging (SE-EPI) sequence. METHODS: A real-time slice-following technique during free-breathing was combined with a sliding acquisition-window strategy prior Principal Component Analysis temporal Maximum Intensity Projection (PCAtMIP) postprocessing of in-plane co-registered diffusion-weighted images. This methodology was applied to 10 volunteers to quantify the performance of the motion correction technique and the reproducibility of diffusion parameters. RESULTS: The slice-following technique offers a powerful head-foot respiratory motion management solution for SE-EPI cDWI with the advantage of a 100% duty cycle scanning efficiency. The level of co-registration was further improved using nonrigid motion corrections and was evaluated with a co-registration index. Vascular fraction f and the diffusion coefficients D and D* were determined to be 0.122 ± 0.013, 1.41 ± 0.09 × 10(-3) mm(2) /s and 43.6 ± 9.2 × 10(-3) mm(2) /s, respectively. From the multidirectional dataset, the measured mean diffusivity was 1.72 ± 0.09 × 10(-3) mm(2) /s and the fractional anisotropy was 0.36 ± 0.02. CONCLUSION: The slice-following DWI SE-EPI sequence is a promising solution for clinical implementation, offering a robust improved workflow for further evaluation of DWI in cardiology. Magn Reson Med 76:70-82, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Algoritmos , Artefatos , Imagem Ecoplanar/métodos , Coração/anatomia & histologia , Interpretação de Imagem Assistida por Computador/métodos , Imagem Cinética por Ressonância Magnética/métodos , Técnicas de Imagem de Sincronização Respiratória/métodos , Adulto , Sistemas Computacionais , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Técnica de Subtração
5.
Magn Reson Med ; 74(4): 990-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25263761

RESUMO

PURPOSE: Although arterial spin labeling (ASL) has become a routinely performed method in the rodent heart, its application to the human heart remains challenged by low tissue blood flow and cardiac and respiratory motion. We hypothesized that an alternative steady-pulsed ASL (spASL) method would provide more efficient perfusion signal averaging by driving the tissue magnetization into a perfusion-dependent steady state. METHODS: We evaluated the feasibility of spASL in the human heart by combining pulsed labeling in the aortic root with a balanced steady state free precession sequence. The spASL scheme was applied to 13 subjects under free breathing. Breathing motion was addressed using retrospective image exclusion based on a contour-based cross-correlation algorithm. RESULTS: The measured signal with spASL was due to labeled blood. We found that the perfusion signal was larger than that obtained with the earlier flow-sensitive alternating inversion recovery (FAIR) method. Averaged myocardial blood flow (MBF) over four myocardial regions was 1.28 ± 0.36 mL·g(-1) ·min(-1) . CONCLUSION: spASL was able to quantify MBF in healthy subjects under free breathing. Because quantification with ASL is more direct than with first-pass perfusion MRI, it appears particularly suited for pathologies with diffuse microvascular alterations, MBF reserve, and follow-up studies.


Assuntos
Circulação Coronária/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Imagem de Perfusão do Miocárdio/métodos , Adulto , Feminino , Humanos , Masculino , Processamento de Sinais Assistido por Computador , Marcadores de Spin , Adulto Jovem
6.
Magn Reson Med ; 73(6): 2195-203, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25046558

RESUMO

PURPOSE: A promise of ultra high field MRI is to produce images of the human brain with higher spatial resolution due to an increased signal to noise ratio. Yet, the shorter radiofrequency wavelength induces an inhomogeneous distribution of the transmit magnetic field and thus challenges the applicability of MRI sequences which rely on the spin excitation homogeneity. In this work, the ability of parallel-transmission to obtain high-quality T2 -weighted images of the human brain at 7 Tesla, using an original pulse design method is evaluated. METHODS: Excitation and refocusing square pulses of a SPACE sequence were replaced with short nonselective transmit-SENSE pulses individually tailored with the gradient ascent pulse engineering algorithm, adopting a kT -point trajectory to simultaneously mitigate B1 (+) and ΔB0 nonuniformities. RESULTS: In vivo experiments showed that exploiting parallel-transmission at 7T with the proposed methodology produces high quality T2 -weighted whole brain images with uniform signal and contrast. Subsequent white and gray matter segmentation confirmed the expected improvements in image quality. CONCLUSION: This work demonstrates that the adopted formalism based on optimal control, combined with the kT -point method, successfully enables three-dimensional T2 -weighted brain imaging at 7T devoid of artifacts resulting from B1 (+) inhomogeneity.


Assuntos
Mapeamento Encefálico/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Artefatos , Humanos , Processamento de Imagem Assistida por Computador/métodos
7.
Radiology ; 271(2): 524-33, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24475838

RESUMO

PURPOSE: To assess time-resolved spin-labeled (SL) magnetic resonance (MR) angiographic imaging with a large acquisition time window over two cardiac cycles for characterization of cerebral arteriovenous malformations (AVMs). MATERIALS AND METHODS: This study was institutional review board-approved. Sixteen patients presented with an AVM, provided informed consent, and were prospectively included. Time-resolved SL MR angiographic images with acquisition window that covered two cardiac cycles (acquisition time, 10-12 min; temporal resolution, 60 msec) or one cardiac cycle and time-of-flight (TOF) MR angiographic images were acquired with a 3-T MR imager. A diagnostic confidence index was used for image quality evaluation; scores were 0, no diagnosis, to 3, high image quality. AVM characterization consisted of arterial feeder, nidus size, and venous drainage type identification compared with those at digital subtraction angiography (DSA). κ coefficients were computed to determine interobserver and intermodality agreement. RESULTS: Time-resolved SL MR angiographic imaging over two cardiac cycles provided a median diagnostic confidence index of 2.5 for arterial feeders, 3.0 for nidus, and 3.0 for venous drainage. Venous drainage depiction quality was higher with time-resolved SL MR angiography over two cardiac cycles than with time-resolved SL MR angiography over one cardiac cycle (P < .001) and TOF MR angiography (P < .001). For AVM characterization, interobserver agreement was very good to excellent, and agreement with DSA showed κ of 0.85 for arterial feeders, κ of 1.00 for nidus size, and κ of 0.82 for venous drainage. CONCLUSION: Time-resolved SL MR angiographic imaging over two cardiac cycles is a reliable clinical tool for cerebral AVM characterization, which showed very good to excellent agreement with DSA.


Assuntos
Malformações Arteriovenosas Intracranianas/diagnóstico , Angiografia por Ressonância Magnética/métodos , Adulto , Idoso , Angiografia Digital , Meios de Contraste , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Marcadores de Spin , Fatores de Tempo , Ácidos Tri-Iodobenzoicos
8.
J Neurosci Res ; 92(4): 432-45, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24446187

RESUMO

Cochlear ablation triggers cellular and molecular reactions in the adult mammalian central auditory system, leading to complex rearrangements in the cellular networks of the auditory brainstem. The role of microglial cells in these processes is largely unknown. We analyzed morphological and molecular responses as well as cellular affiliations of microglia in the auditory brainstem 1 and 7 days after unilateral sensory deafferentation of the cochlear nucleus. In the ventral cochlear nucleus (VCN), morphological changes of microglial cells were evident following cochlear ablation. Microglial activation preceded astroglial hypertrophy in VCN and lateral superior olive (LSO). During axonal degeneration in VCN early after cochlear ablation, p-ERK1/2- and p-p38-immunoreactive microglia displayed a hypertrophied phenotype, with processes partially surrounding glutamatergic but not GABAergic synapses. During the peak of VCN reinnervation 1 week after cochlear ablation, the number of microglial cells increased massively. Microglia now displayed dense ramifications juxtaposed to Gap43-immunoreactive axons and their terminals. Moreover, we identified lesion-dependent changes in the populations of microglia and astrocytes in LSO and inferior colliculus. By covisualizing cytological markers such as NeuN, GFAP, CD11b, vGluT-1, GAD-65, and Gap43 with the prominent MAP kinases ERK1/2 and p38, we show that MAPK signaling is affected by sensory deafferentation in microglia but not in astroglia or in neurons. In conclusion, microglia displaying MAPK signaling appear to contribute to an adaptive response in central auditory regions that was directly or indirectly affected by sensory deafferentation. Moreover, microglial cells are temporally and spatially in place to participate in synaptogenesis inside VCN.


Assuntos
Núcleo Coclear/citologia , Microglia/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Cóclea/inervação , Cóclea/cirurgia , Nervo Coclear/citologia , Nervo Coclear/fisiologia , Denervação , Feminino , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Wistar
9.
J Nucl Cardiol ; 21(1): 192-220, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24374980

RESUMO

The American College of Cardiology Foundation along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical presentations for stable ischemic heart disease (SIHD) to consider use of stress testing and anatomic diagnostic procedures. This document reflects an updating of the prior Appropriate Use Criteria (AUC) published for radionuclide imaging (RNI), stress echocardiography (Echo), calcium scoring, coronary computed tomography angiography (CCTA), stress cardiac magnetic resonance (CMR), and invasive coronary angiography for SIHD. This is in keeping with the commitment to revise and refine the AUC on a frequent basis. A major innovation in this document is the rating of tests side by side for the same indication. The side-by-side rating removes any concerns about differences in indication or interpretation stemming from prior use of separate documents for each test. However, the ratings were explicitly not competitive rankings due to the limited availability of comparative evidence, patient variability, and range of capabilities available in any given local setting. The indications for this review are limited to the detection and risk assessment of SIHD and were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Eighty clinical scenarios were developed by a writing committee and scored by a separate rating panel on a scale of 1-9, to designate Appropriate, May Be Appropriate, or Rarely Appropriate use following a modified Delphi process following the recently updated AUC development methodology. The use of some modalities of testing in the initial evaluation of patients with symptoms representing ischemic equivalents, newly diagnosed heart failure, arrhythmias, and syncope was generally found to be Appropriate or May Be Appropriate, except in cases where low pre-test probability or low risk limited the benefit of most testing except exercise electrocardiogram (ECG). Testing for the evaluation of new or worsening symptoms following a prior test or procedure was found to be Appropriate. In addition, testing was found to be Appropriate or May Be Appropriate for patients within 90 days of an abnormal or uncertain prior result. Pre-operative testing was rated Appropriate or May Be Appropriate only for patients who had poor functional capacity and were undergoing vascular or intermediate risk surgery with 1 or more clinical risk factors or an organ transplant. The exercise ECG was suggested as an Appropriate test for cardiac rehabilitation clearance or for exercise prescription purposes. Testing in asymptomatic patients was generally found to be Rarely Appropriate, except for calcium scoring and exercise testing in intermediate and high-risk individuals and either stress or anatomic imaging in higher-risk individuals, which were all rated as May Be Appropriate. All modalities of follow-up testing after a prior test or percutaneous coronary intervention (PCI) within 2 years and within 5 years after coronary artery bypass graft (CABG) in the absence of new symptoms were rated Rarely Appropriate. Pre-operative testing for patients with good functional capacity, prior normal testing within 1 year, or prior to low-risk surgery also were found to be Rarely Appropriate. Imaging for an exercise prescription or prior to the initiation of cardiac rehabilitation was Rarely Appropriate except for cardiac rehabilitation clearance for heart failure patients.


Assuntos
Cardiologia/normas , Angiografia Coronária/normas , Isquemia Miocárdica/terapia , Adulto , Idoso , Algoritmos , American Heart Association , Tomada de Decisões , Exercício Físico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Segurança do Paciente , Medição de Risco , Sociedades Médicas , Resultado do Tratamento , Estados Unidos
10.
Eur J Neurosci ; 38(1): 2041-56, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23581580

RESUMO

Ablating the cochlea causes total sensory deafferentation of the cochlear nucleus. Over the first postoperative week, degeneration of the auditory nerve and its synaptic terminals in the cochlear nucleus temporally overlaps with its re-innervation by axon collaterals of medial olivocochlear neurons. At the same time, astrocytes increase in size and density. We investigated the time courses of the expression of ezrin, polysialic acid, matrix metalloprotease-9 and matrix metalloprotease-2 within these astrocytes during the first week following cochlear ablation. All four proteins are known to participate in degeneration, regeneration, or both, following injury of the central nervous system. In a next step, stereotaxic injections of kainic acid were made into the ventral nucleus of the trapezoid body prior to cochlear ablation to destroy the neurons that re-innervate the deafferented cochlear nucleus by axon collaterals developing growth-associated protein 43 immunoreactivity. This experimental design allowed us to distinguish between molecular processes associated with degeneration and those associated with re-innervation. Under these conditions, astrocytic growth and proliferation showed an unchanged deafferentation-induced pattern. Similarly, the distribution and amount of ezrin and matrix metalloprotease-9 in astrocytes after cochlear ablation developed in the same way as under cochlear ablation alone. In sharp contrast, the astrocytic expression of polysialic acid and matrix metalloprotease-2 normally invoked by cochlear ablation collapsed when re-innervation of the cochlear nucleus was inhibited by lesioning medial olivocochlear neurons with kainic acid. In conclusion, re-innervation, including axonal growth and synaptogenesis, seems to prompt astrocytes to recompose their molecular profile, paving the way for tissue reorganisation after nerve degeneration and loss of synaptic contacts.


Assuntos
Astrócitos/metabolismo , Núcleo Coclear/fisiologia , Neurônios Aferentes/fisiologia , Animais , Astrócitos/fisiologia , Axônios/efeitos dos fármacos , Axônios/fisiologia , Proliferação de Células , Cóclea/inervação , Nervo Coclear/citologia , Nervo Coclear/fisiologia , Núcleo Coclear/citologia , Núcleo Coclear/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Denervação , Feminino , Proteína GAP-43/genética , Proteína GAP-43/metabolismo , Ácido Caínico/toxicidade , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Regeneração Nervosa , Neurônios Aferentes/efeitos dos fármacos , Ratos , Ratos Wistar , Ácidos Siálicos/metabolismo
11.
Heliyon ; 9(4): e15000, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37089322

RESUMO

Urban areas are the engines of socioeconomic growth and the homes of billions of people around the globe. In a changing climate, urban areas are inexorably from vulnerability to climate hazards including flooding which deters their social, economic, and environmental sustainability. The main objective of this paper was to explore exposure to elements at risk due to climate change-induced flooding in urban areas. In addition, the paper analyses the coping and adaptation strategies practiced at the community and national levels and recommends appropriate policy measures for enhanced climate resilience in urban areas. The study adopted purposeful sampling in which n = 95 households were selected for the study. Data collection methods involved household interviews with structured questionnaires, focused group discussions, documentary reviews, transect walks, surveys, and observations. Data analysis was done with a statistical package for social sciences. The results revealed that the elements at risk of exposure to climate change-induced flooding in the study area were physical infrastructures, socio-economic activities, livelihoods, and ecosystems. The study recommends enhancing resilience of elements at risk to climate change-induced flooding at national and local levels in urban areas. This is through promoting flood policies, strategies, laws, planning and management measures; enhance non-structural actions including flood forecasting, mapping, emergency evacuation plans and land use zoning and structural measures namely dams, dikes, storm surge barriers for adaptation to urban flooding.

12.
Cells ; 11(10)2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35626639

RESUMO

Social behavior is a basic domain affected by several neurodevelopmental disorders, including ASD and a heterogeneous set of neuropsychiatric disorders. The SCRIB gene that codes for the polarity protein SCRIBBLE has been identified as a risk gene for spina bifida, the most common type of neural tube defect, found at high frequencies in autistic patients, as well as other congenital anomalies. The deletions and mutations of the 8q24.3 region encompassing SCRIB are also associated with multisyndromic and rare disorders. Nonetheless, the potential link between SCRIB and relevant social phenotypes has not been fully investigated. Hence, we show that Scribcrc/+ mice, carrying a mutated version of Scrib, displayed reduced social motivation behavior and social habituation, while other behavioral domains were unaltered. Social deficits were associated with the upregulation of ERK phosphorylation, together with increased c-Fos activity. Importantly, the social alterations were rescued by both direct and indirect pERK inhibition. These results support a link between polarity genes, social behaviors and hippocampal functionality and suggest a role for SCRIB in the etiopathology of neurodevelopmental disorders. Furthermore, our data demonstrate the crucial role of the MAPK/ERK signaling pathway in underlying social motivation behavior, thus supporting its relevance as a therapeutic target.


Assuntos
Sistema de Sinalização das MAP Quinases , Motivação , Animais , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Mutação , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Comportamento Social
13.
Neural Plast ; 2011: 859359, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22135757

RESUMO

The matrix metalloproteinases MMP-9 and MMP-2, major modulators of the extracellular matrix (ECM), were changed in amount and distribution in the rat anteroventral cochlear nucleus (AVCN) following its sensory deafferentation by cochlear ablation. To determine what causal relationships exist between the redistribution of MMP-9 and MMP-2 and deafferentation-induced reinnervation, kainic acid was stereotaxically injected into the ventral nucleus of the trapezoid body (VNTB) prior to cochlear ablation, killing cells that deliver the growth associated protein 43 (GAP-43) into AVCN. Deafferentation-induced changes in the pattern of MMP-9 staining remained unaffected by VNTB lesions. By contrast, changes in the distribution of MMP-2 normally evoked by sensory deafferentation were reversed if GAP-43 positive axons were prevented to grow in AVCN. In conclusion, GAP-43-containing axons emerging in AVCN after cochlear ablation seem to be causal for the maintenance of MMP-2-mediated ECM remodeling.


Assuntos
Axônios/metabolismo , Núcleo Coclear/enzimologia , Proteína GAP-43/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Animais , Núcleo Coclear/metabolismo , Ácido Caínico/administração & dosagem , Cinética , Ratos
14.
Cell Rep ; 31(10): 107743, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32521268

RESUMO

The organization of spatial information, including pattern completion and pattern separation processes, relies on the hippocampal circuits, yet the molecular and cellular mechanisms underlying these two processes are elusive. Here, we find that loss of Vangl2, a core PCP gene, results in opposite effects on pattern completion and pattern separation processes. Mechanistically, we show that Vangl2 loss maintains young postmitotic granule cells in an immature state, providing increased cellular input for pattern separation. The genetic ablation of Vangl2 disrupts granule cell morpho-functional maturation and further prevents CaMKII and GluA1 phosphorylation, disrupting the stabilization of AMPA receptors. As a functional consequence, LTP at lateral perforant path-GC synapses is impaired, leading to defects in pattern completion behavior. In conclusion, we show that Vangl2 exerts a bimodal regulation on young and mature GCs, and its disruption leads to an imbalance in hippocampus-dependent pattern completion and separation processes.


Assuntos
Giro Denteado/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Polaridade Celular/fisiologia , Giro Denteado/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Fosforilação , Receptores de AMPA/metabolismo
15.
Magn Reson Med ; 62(5): 1155-63, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19780150

RESUMO

Typically, MR-elastography (MRE) encodes the propagation of monochromatic acoustic waves in the MR-phase images via sinusoidal gradients characterized by a detection frequency equal to the frequency of the mechanical vibration. Therefore, the echo time of a conventional MRE sequence is typically longer than the vibration period which is critical for heart tissue exhibiting a short T(2). Thus, fast acquisition techniques like the so-called fractional encoding of harmonic motions were developed for cardiac applications. However, fractional encoding of harmonic motions is limited since it is two orders of magnitude less sensitive to motion than conventional MRE sequences for low-frequency vibrations. Here, a new sequence is derived from the so-called displacement encoding with stimulated echoes (DENSE) sequence. This sequence is more sensitive to displacement than fractional encoding of harmonic motions, and its spectral specificity is equivalent to conventional MRE sequences. The theoretical spectral properties of this new motion-encoding technique are validated in a phantom and excised pork heart specimen. An excellent agreement is found for the measured displacement fields using classic MRE and displacement encoding with stimulated echoes MRE (8% maximum difference). In addition, initial in vivo results on a healthy volunteer clearly show propagating shear waves at 50 Hz. Thus, displacement encoding with stimulated echoes MRE is a promising technique for motion encoding within short T(2)* materials.


Assuntos
Algoritmos , Técnicas de Imagem por Elasticidade/métodos , Coração/anatomia & histologia , Coração/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Módulo de Elasticidade/fisiologia , Técnicas de Imagem por Elasticidade/instrumentação , Humanos , Aumento da Imagem/métodos , Imagens de Fantasmas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
J Card Fail ; 20(2): 65-90, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24556531
17.
Exp Brain Res ; 195(2): 241-60, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19340418

RESUMO

The nuclei of the auditory brainstem harbor a diversity of neuronal cell types and are interconnected by excitatory as well as inhibitory ascending, descending, and commissural pathways. Classically, neurons have been characterized by size and shape of their cell body and by the geometry of their dendrites. Our study is based on the use of axonal tracers in combination with immunocytochemistry to identify and distinguish neuronal subtypes by their molecular signature in dorsal and ventral cochlear nucleus, lateral superior olive, medial superior olive, medial nucleus of the trapezoid body, and inferior colliculus of the adult rat. The presumed neurotransmitters glutamate, glycine, and GABA were used alongside the calcium-binding proteins parvalbumin, calretinin, and calbindin-D28k as molecular markers. Our data provide distinct extensions to previous characterizations of neuronal subtypes and reveal regularities and differences across auditory brainstem nuclei that are discussed for their functional implications.


Assuntos
Vias Auditivas/citologia , Axônios/fisiologia , Tronco Encefálico/citologia , Neurônios/citologia , Neurônios/fisiologia , Animais , Vias Auditivas/anatomia & histologia , Vias Auditivas/fisiologia , Tronco Encefálico/anatomia & histologia , Tronco Encefálico/fisiologia , Calbindina 1 , Calbindina 2 , Calbindinas , Fluorescência , Ácido Glutâmico/metabolismo , Glicina/metabolismo , Imuno-Histoquímica , Microscopia de Fluorescência , Parvalbuminas/metabolismo , Ratos , Ratos Wistar , Proteína G de Ligação ao Cálcio S100/metabolismo , Ácido gama-Aminobutírico/metabolismo
18.
Alcohol Alcohol ; 44(4): 423-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19482879

RESUMO

AIM: The aim of this study was to describe the feasibility, advantages and limitations of the combined use of Internet and SMS technology to assess alcohol use, and to test whether an SMS sent in the evening (i.e. prior to a possible drinking event) changed the respondents' assessment, made on the following day, of the number of drinks consumed. PARTICIPANTS: Seventy young adults (mean age 22.7) were recruited through face-to-face contacts, e-mails and Internet advertisements. DESIGN AND SETTING: Participants completed a baseline assessment via Internet and were randomly assigned to two conditions (with and without evening SMS). Over four weekends, both Friday and Saturday night, drinking was assessed via SMS questions sent the next day to the participants' cell phones. RESULTS: A high retention rate (75% in total) was obtained across all three recruitment conditions. The number of drinks indicated in the SMS survey was strongly correlated with the usual quantity assessed via Internet and did not differ depending on whether an additional SMS question was sent in the evening or not. CONCLUSION: The new method shares some of the advantages of conventional diaries but overcomes most of the limitations: it is easy to use, cost-effective and suitable for large-scale surveys. Application restrictions and further developments are discussed.


Assuntos
Alcoolismo/psicologia , Correio Eletrônico , Pesquisa/instrumentação , Adolescente , Adulto , Análise Custo-Benefício , Estudos de Viabilidade , Feminino , Humanos , Internet , Masculino , Inquéritos e Questionários , Adulto Jovem
19.
Brain Behav ; 9(8): e01353, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31271523

RESUMO

INTRODUCTION: Cochlear ablation causing sensory deafferentation (SD) of the cochlear nucleus triggers complex re-arrangements in the cellular and molecular communication networks of the adult mammalian central auditory system. Participation of the extracellular matrix (ECM) in these processes is not well understood. METHODS: We investigated consequences of unilateral SD for the expression and distribution of the chondroitin sulfate proteoglycans, neurocan (Ncan) and aggrecan (Agg), alongside various plasticity markers in the auditory brainstem of the adult rat using immunohistochemical techniques. RESULTS: In the deafferented ventral cochlear nucleus (VCN), Ncan expression increased massively within 3 postoperative days (POD), but rapidly decreased thereafter. Agg showed a similar but less pronounced progression. Decrease in Ncan was spatially and temporally related to the re-innervation of VCN documented by the emergence of growth-associated protein Gap43 contained in nerve fibers and presynaptic boutons. Concurrently, astrocytes grew and expressed matrix metalloproteinase-2 (MMP2), an enzyme known to emerge only under re-innervation of VCN. MMP2 is capable of cleaving both Ncan and Agg when released. A transient modulation of the ECM in the central inferior colliculus on the side opposite to SD occurred by POD1. Modulations of glutamatergic synapses and Gap43 expression were detected, reflecting state changes of the surrounding tissue induced by transsynaptic effects of SD. CONCLUSIONS: The ECM variously participates in adaptive responses to sudden deafness by SD on several levels along the central auditory pathway, with a striking spatial and temporal relationship of Ncan modulation to astrocytic activation and to synaptogenesis.


Assuntos
Astrócitos/metabolismo , Vias Auditivas/metabolismo , Tronco Encefálico/metabolismo , Núcleo Coclear/metabolismo , Neurocam/metabolismo , Vias Aferentes/metabolismo , Agrecanas/metabolismo , Animais , Feminino , Metaloproteinase 2 da Matriz/metabolismo , Neurogênese/fisiologia , Ratos , Ratos Wistar
20.
Neuroscience ; 400: 1-16, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30594562

RESUMO

Worldwide, almost 500 million people are hearing impaired, making hearing loss the most common sensory impairment among humans. For people with single-sided deafness (SSD), cochlear implants (CIs) can be enormously beneficial by providing binaural information. However, binaural benefits in CI users have been only incompletely realized. Overcoming these limitations requires a better knowledge of how neuronal circuits adapt to SSD and how unilateral CI stimulation can compensate a deaf ear. We investigated effects of neonatal SSD on auditory brainstem circuitry using acoustic (AS), electric (ES), or acoustic stimulation on one ear and electric stimulation on the other ear (AS + ES). The molecular marker Fos was used to investigate changes in interneuronal communication due to SSD. To induce SSD, neonatal rats obtained a unilateral intracochlear injection of neomycin. In adulthood, rats were acutely stimulated by AS, ES, or AS + ES. AS and ES were applied correspondingly in terms of intracochlear stimulation side and intensity resulting in bilaterally comparable Fos expression in hearing rats. In contrast, SSD rats showed a loss of tonotopic order along the deafened pathway, indicated by a massive increase and spread of Fos expressing neurons. We report three major results: First, AS of the hearing ear of SSD rats resulted in bilateral activation of neurons in the cochlear nucleus (CN). Second, ES of the deaf ear did not activate contralateral CN. Third, AS + ES of SSD rats resulted in bilateral reduced Fos expression in the auditory brainstem compared to monaural stimulations. These findings indicate changes in inhibitory interactions among neuronal networks as a result of monaural deafness.


Assuntos
Núcleo Coclear/fisiopatologia , Surdez/fisiopatologia , Neurônios/fisiologia , Estimulação Acústica , Animais , Vias Auditivas/fisiopatologia , Implante Coclear , Estimulação Elétrica , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Lateralidade Funcional , Masculino , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar
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