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1.
Int J Mol Sci ; 25(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38396950

RESUMO

The complement is a component of the innate immune system designed to fight infections and tissue- or age-related damages. Complement activation creates an inflammatory microenvironment, which enhances cell death. Excessive complement inflammatory activity has been linked to alterations in the structure and functions of the blood-brain barrier, contributing to a poor prognosis for Alzheimer's disease (AD). In the AD preclinical phase, individuals are often clinically asymptomatic despite evidence of AD neuropathology coupled with heightened inflammation. Considering the involvement of the complement system in the risk of developing AD, we hypothesize that inhibiting complement activation could reduce this inflammatory period observed even before clinical signs, thereby slowing down the onset/progression of AD. To validate our hypothesis, we injected complement inhibitor factor H into the brain of APP/PS1 AD mice at early or late stages of this pathology. Our results showed that the injection of factor H had effects on both the onset and progression of AD by reducing proinflammatory IL6, TNF-α, IL1ß, MAC and amyloid beta levels. This reduction was associated with an increase in VGLUT1 and Psd95 synaptic transmission in the hippocampal region, leading to an improvement in cognitive functions. This study invites a reconsideration of factor H's therapeutic potential for AD treatment.


Assuntos
Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Fator H do Complemento , Camundongos Transgênicos , Ativação do Complemento , Modelos Animais de Doenças
2.
Sensors (Basel) ; 21(22)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34833514

RESUMO

The aim of this study was to establish an accessible methodology for the objective identification and 3D morphological characterization of renal glomeruli in mice. 3D imaging of the renal cortex was performed by light sheet microscopy on iDISCO+ optical cleared kidneys of six C57BL/6J mice after labelling of the capillary endothelium by lectin injection. 3D images were processed with the open source software ImageJ, and statistical analysis done with GraphPad Prism. Non-visual delimitation of the external surface of the glomeruli was ensured by greyscale-based thresholding, the value of which was determined from the statistical analysis of the voxel frequency distribution. Exclusion of false-positive identification was done by successive volume- and shape-based segmentation. Renal glomeruli were characterized by their number, surface area, volume, and compactness. Average data were expressed as mean ± SD. The number of glomeruli was equal to 283 ± 35 per mm3 of renal tissue, representing 1.78 ± 0.49% of the tissue volume. The surface area, volume and compactness were equal to 20,830 ± 6200 µm², 62,280 ± 14,000 µm3 and 0.068 ± 0.026, respectively. The proposed standardized methodology allows the identification of the renal glomeruli and their 3D morphological characterization, and is easily accessible for biologists.


Assuntos
Glomérulos Renais , Rim , Animais , Imageamento Tridimensional , Camundongos , Camundongos Endogâmicos C57BL , Microscopia
3.
Front Physiol ; 15: 1386151, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39072218

RESUMO

Introduction: Blood flow produces fluid shear stress (SS), a frictional force parallel to the blood flow, on the endothelial cell (EC) layer of the lumen of the vessels. ECs themselves are sensitive to this frictional force in terms of directionality and intensity. The aim of this study was to determine the physiological shear stress value during the cardiac cycle and EC polarity and orientation from blood flow in healthy male and female mouse carotid artery. Methods: Experimentation is done on anesthetized male and female 8-week-old C5BL/6J mice. In vivo measurements of maximum blood velocity and vessel diameter in diastole and systole were performed on the right common carotid artery by Doppler ultrasound imaging. Blood viscosity (total and plasmatic) and hematocrit were determined on blood samples. For SS calculation, we developed a new method assuming heterogenous blood flow, i.e., a red cell central plug flow surrounded by a peripheral plasma sheath flow, and computing SS from vessel diameter and hemodynamical measurements (maximal blood velocity, hematocrit and plasmatic viscosity). Results: Results were compared with the classical method assuming a homogenous blood flow with constant apparent total blood viscosity. EC polarity and orientation were determined ex vivo on the carotid endothelium by confocal imaging after labeling of the EC nucleus and Golgi apparatus. Diastolic and systolic SS were 6 ± 2.5 Pa and 30 ± 6.5 Pa, respectively. Total blood and plasmatic viscosity was 4 ± 0.5 cP and 1.27 cP, respectively. ECs were polarized and significantly oriented against blood flow. No sex difference was identified.

4.
iScience ; 26(10): 108007, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37810224

RESUMO

The vascular system is a multi-scale network whose functionality depends on its structure, and for which structural alterations can be linked to pathological shifts. Though biologists use multiple 3D imaging techniques to visualize vascular networks, the 3D image processing methodologies remain sources of biases, and the extraction of quantitative morphometric descriptors remains flawed. The article, first, reviews the current 3D image processing methodologies, and morphometric descriptors of vascular network images mainly obtained by light-sheet microscopy on optically cleared organs, found in the literature. Second, it proposes operator-independent segmentation and skeletonization methodologies using the freeware ImageJ. Third, it gives more extractable network-level (density, connectivity, fractal dimension) and segment-level (length, diameter, tortuosity) 3D morphometric descriptors and how to statistically analyze them. Thus, it can serve as a guideline for biologists using 3D imaging techniques of vascular networks, allowing the production of more comparable studies in the future.

5.
Biology (Basel) ; 10(4)2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33917130

RESUMO

Characterization of the cardiac capillary network structure is of critical importance to understand the normal coronary functional properties and coronary microvascular diseases. The aim of our study was to establish an accessible methodology for 3D imaging and 3D processing to quantitatively characterize the capillary coronary network architecture in mice. Experiments were done on C57BL/6J mice. 3D imaging was performed by light sheet microscopy and confocal microscopy on iDISCO+ optical cleared hearts after labelling of the capillary endothelium by lectin injection. 3D images were processed with the open source software ImageJ. Non-visual image segmentation was based of the frequency distribution of the voxel greyscale values, followed by skeletonization and distance mapping. Capillary networks in left and right ventricles and septum were characterized by the volume network density, the fractal dimension, the number of segments and nodes and their ratio, the total network length, and the average length, diameter, and tortuosity of the segments. Scale-dependent parameter values can be impacted by the resolution limit of the 3D imaging technique. The proposed standardized methodology for 3D image processing is easily accessible for a biologist in terms of investment and difficulty level, and allows the quantification of the 3D capillary architecture and its statistical comparison in different conditions.

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