Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models.

Cerebral blood flow (CBF) reductions in Alzheimer’s disease patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences for Alzheimer’s disease pathogenesis remain poorly understood. In APP/PS1 and 5xFAD mice we found that an increased number of cortical capillaries had stalled blood flow as compared to in wild-type animals, largely due to neutrophils that had adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to both an immediate increase in CBF and rapidly improved performance in spatial and working memory tasks. This study identified a previously uncharacterized cellular mechanism that explains the majority of the CBF reduction seen in two mouse models of Alzheimer’s disease and demonstrated that improving CBF rapidly enhanced short-term memory function. Restoring cerebral perfusion by preventing neutrophil adhesion may provide a strategy for improving cognition in Alzheimer’s disease patients

La radiothérapie assistée par l’imagerie nucléaire : les volumes cibles

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FDG-PET imaging for radiotherapy target volume definition in lung cancer

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Monte-Carlo simulations of clinically realistic respiratory gated (18)F-FDG PET: application to lesion detectability and volume measurements.

International audienceIn PET/CT thoracic imaging, respiratory motion reduces image quality. A solution consists in performing respiratory gated PET acquisitions. The aim of this study was to generate clinically realistic Monte-Carlo respiratory PET data, obtained using the 4D-NCAT numerical phantom and the GATE simulation tool, to assess the impact of respiratory motion and respiratory-motion compensation in PET on lesion detection and volume measurement. To obtain reconstructed images as close as possible to those obtained in clinical conditions, a particular attention was paid to apply to the simulated data the same correction and reconstruction processes as those applied to real clinical data. The simulations required 140,000h (CPU) generating 1.5 To of data (98 respiratory gated and 49 ungated scans). Calibration phantom and patient reconstructed images from the simulated data were visually and quantitatively very similar to those obtained in clinical studies. The lesion detectability was higher when the better trade-off between lesion movement limitation (compared to ungated acquisitions) and image statistic preservation is considered (respiratory cycle sampling in 3 frames). We then compared the lesion volumes measured on conventional PET acquisitions versus respiratory gated acquisitions, using an automatic segmentation method and a 40%-threshold approach. A time consuming initial manual exclusion of noisy structures needed with the 40%-threshold was not necessary when the automatic method was used. The lesion detectability along with the accuracy of tumor volume estimates was largely improved with the gated compared to ungated PET images

Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer's disease mouse models.

Cerebral blood flow (CBF) reductions in Alzheimer's disease patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences for Alzheimer's disease pathogenesis remain poorly understood. In APP/PS1 and 5xFAD mice we found that an increased number of cortical capillaries had stalled blood flow as compared to in wild-type animals, largely due to neutrophils that had adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to both an immediate increase in CBF and rapidly improved performance in spatial and working memory tasks. This study identified a previously uncharacterized cellular mechanism that explains the majority of the CBF reduction seen in two mouse models of Alzheimer's disease and demonstrated that improving CBF rapidly enhanced short-term memory function. Restoring cerebral perfusion by preventing neutrophil adhesion may provide a strategy for improving cognition in Alzheimer's disease patients

Data from: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models

If you use these data, please cite the original authors. Suggested citation: Hernandez, et al. (2019). Data from: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models [Dataset]. Cornell University Library eCommons Repository. https://doi.org/10.7298/9PR3-D773.Cerebral blood flow (CBF) reductions in Alzheimer’s disease (AD) patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences on AD pathogenesis remain poorly understood. In APP/PS1 and 5xFAD mice we found that an increased number of cortical capillaries had stalled blood flow as compared to wildtype animals, largely due to neutrophils that adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to an immediate increase in CBF and to rapidly improved performance in spatial and working memory tasks. This study identified a novel cellular mechanism that explains the majority of the CBF reduction seen in two mouse models of AD and demonstrated that improving CBF rapidly improved short-term memory function. Restoring cerebral perfusion by preventing neutrophil adhesion may provide a novel strategy for improving cognition in AD patients. This dataset supports the above research and conclusions.This work was supported by the National Institutes of Health grants Nos. AG049952 (C.B.S.), NS37853 (CI) and AG031620 (N.N.), the Alzheimer’s Drug Discovery Foundation (C.B.S.), the Alzheimer’s Art Quilt Initiative (C.B.S.), the BrightFocus Foundation (C.B.S.), European Research Council grant No. 615102 (S.L.), the DFG German Research Foundation (O.B.), a National Science Foundation Graduate Research Fellowship (J.C.H.), the L’Oréal Fellowship for Women in Science (N.N.) and used computing resources at CALMIP (S.L.)

Microbubble moving in blood flow in microchannels: effect on the cell-free layer and cell local concentration

Gas embolisms can hinder blood flow and lead to occlusion of the vessels and ischemia. Bubbles in microvessels circulate as tubular bubbles (Taylor bubbles) and can be trapped, blocking the normal flow of blood. To understand how Taylor bubbles flow in microcirculation, in particular, how bubbles disturb the blood flow at the scale of blood cells, experiments were performed in microchannels at a low Capillary number. Bubbles moving with a stream of in vitro blood were filmed with the help of a high-speed camera. Cell-free layers (CFLs) were observed downstream of the bubble, near the microchannel walls and along the centerline, and their thicknesses were quantified. Upstream to the bubble, the cell concentration is higher and CFLs are less clear. While just upstream of the bubble the maximum RBC concentration happens at positions closest to the wall, downstream the maximum is in an intermediate region between the centerline and the wall. Bubbles within microchannels promote complex spatio-temporal variations of the CFL thickness along the microchannel with significant relevance for local rheology and transport processes. The phenomenon is explained by the flow pattern characteristic of low Capillary number flows. Spatio-temporal variations of blood rheology may have an important role in bubble trapping and dislodging.The authors acknowledge the financial support provided by PTDC/SAU-BEB/105650/2008, PTDC/SAU-ENB/ 116929/2010, EXPL/EMS-SIS/2215/2013 and PTDC/QEQ-FTT/4287/ 2014 from FCT (Science and Technology Foundation), COMPETE, QREN and European Union (FEDER).info:eu-repo/semantics/publishedVersio