Biology subjects

Wiart, M.

Publications and source records attributed to Wiart, M..

8 recordsLinked to original sources

bioRxiv2024

Reduced Folate Carrier 1 (RFC1/Slc19a1) Suppression Exacerbates Blood-Brain Barrier Breakdown in Experimental Ischemic Stroke in Adult Mice

The Reduced Folate Carrier 1 (RFC1), also called solute carrier family 19 member 1 (SLC19A1/SLC19a1), is recognized for transporting folates across the blood-brain barrier (BBB). RFC1 has recently been defined as a hypoxia-immune related gene whose expression levels were induced by acute retinal ischemia, suggesting that RFC1 may have a role in the response of the brain to ischemic injury. Despite a recent human meta-analysis suggesting an association between certain RFC1 polymorphisms and the risk of silent brain infarctions, preclinical evidence concerning the potential role of RFC1 in acute ischemic stroke has yet to be presented. To investigate this, we first characterized RFC1 protein expression in mouse microvessels and pericytes which play significant roles in stroke pathophysiology. Then, we examined the temporal (1-h, 24-h, and 48-h) and spatial (infarct, periinfarct, contralateral) expression of RFC1 protein in the intraluminal transient middle cerebral artery occlusion mouse model. Finally, we knocked down RFC1 protein with RFC1-siRNA in the potential periinfarct region before induction of ischemia and investigated BBB integrity and infarct size in vivo via 7T-MRI. Moreover, we utilized a pharmacological modulation-methotrexate, a non-covalent inhibitor of RFC1- to further investigate the role of RFC1 in maintaining BBB integrity. Our study revealed that, i) RFC1 protein levels were dynamic throughout the acute phases of ischemic stroke, ii) RFC1 suppression aggravated the BBB leakage during ischemia. These results emphases the role of RFC1 in the pathophysiology of ischemic stroke and supports the evidence from human studies.

neuroscience↗

bioRxiv2024

MorphoCellSorter: An Andrews plot-based sorting approach to rank microglia according to their morphological features

Microglia exhibit diverse morphologies reflecting environmental conditions, maturity or functional states. Thus, morphological characterization provides important information to understand microglial roles and functions. Most recent morphological analysis relies on classifying cells based on morphological parameters. However, this classification may lack biological relevance, as microglial morphologies represent a continuum rather than distinct, separate groups, and do not correspond to mathematically defined, clusters irrelevant of microglial cells function. Instead, we propose a new open-source tool, MorphoCellSorter, which assesses microglial morphology by automatically computing morphological criteria, using principal component analysis and Andrews plots to rank cells. MorphoCellSorter properly ranked cells from various microglia datasets in mice and rats of different age, from in vivo, in vitro and ex vivo models, that were acquired using diverse imaging techniques. This approach allowed for the discrimination of cell populations in various pathophysiological conditions. Finally, MorphoCellSorter offers a versatile, easy and ready-to-use method to evaluate microglial morphological diversity that could easily be generalized to standardize practices across laboratories.

neuroscience↗

bioRxiv2024

Head down tilt 15° increases cerebral perfusion before recanalization in acute ischemic stroke: a pre-clinical MRI study.

We investigated the therapeutic effect of head down positioning at -15{degrees} (head down tilt; HDT15) on cerebral collateral flow and infarct growth in a rat model of large vessel occlusion (LVO) stroke, using multi-modal MRI. Twenty-eight Wistar rats were randomly assigned to HDT15 or flat position for 60 minutes, starting 30 minutes after occlusion of the middle cerebral artery, followed by reperfusion. The perfusion shift analysis, comparing post- versus pre-treatment voxel-level changes in time-to-peak perfusion maps, showed a significant increase in cerebral perfusion in the HDT15 group (common odds ratio 1.50; 95% CI 1.41-1.60; p < 0.0001), but not in the flat group (common odds ratio 0.97; 95% CI 0.92-1.03; p = 0.3503). Infarct growth at 24 hours was + 31.4% in the flat group (343 versus 250 mm3; 95% CI 2.4 to 165.1; p = 0.0447) and + 15.4% in the HDT15 group (224 versus 192 mm3; 95% CI -26.9 to 85.9; p = 0.2272). Our findings indicate that HDT15 acutely increases cerebral perfusion in LVO acute ischemic stroke and provides a tissue-saving effect before recanalization. Further research is needed to develop HDT15 as an emergency therapy to acutely increase collateral flow in ischemic stroke prior to recanalization therapy.

neuroscience↗

bioRxiv2023

A novel injectable radiopaque hydrogel with potent properties for multicolor CT imaging in the context of brain and cartilage regenerative therapy

Cell therapy is promising to treat many conditions, including neurological and osteoarticular diseases. Encapsulation of cells within hydrogels facilitates cell delivery and can improve therapeutic effects. However, much work remains to be done to align treatment strategies with specific diseases. The development of imaging tools that enable monitoring cells and hydrogel independently is key to achieving this goal. Our objective herein is to longitudinally study an iodine-labeled hydrogel, incorporating gold-labeled stem cells, by bicolor CT imaging after in vivo injection in rodent brains or knees. To this aim, an injectable self-healing hyaluronic acid (HA) hydrogel with long-persistent radiopacity was formed by the covalent grafting of a clinical contrast agent on HA. The labeling conditions were tuned to achieve sufficient X-ray signal and to maintain the mechanical and self-healing properties as well as injectability of the original HA scaffold. The efficient delivery of both cells and hydrogel at the targeted sites was demonstrated by synchrotron K-edge subtraction-CT. The iodine labeling enabled to monitor the hydrogel biodistribution in vivo up to 3 days post-administration, which represents a technological first in the field of molecular CT imaging agents. This tool may foster the translation of combined cell-hydrogel therapies into the clinics.

bioengineering↗

bioRxiv2023

PREMISE: A database of 20 Macaca Fascicularis PET/MRI brain imaging available for research

Non-human primate (NHP) studies are unique in translational research, especially in neurosciences and neuroimaging approaches are a preferred method for scaling cross-species comparative neurosciences. In this regard, neuroimaging database development and sharing are encouraged to increase the number of subjects available to the community while limiting the number of animals used in research. We present here a simultaneous PET/MR dataset of 20 Macaca Fascicularis structured according to the Brain Imaging Data Structure (BIDS) standards. This database contains multiple MRI sequences (anatomical, diffusion and perfusion imaging notably), as well as PET perfusion and inflammation using respectively [15O]H2O and [11C]PK11195 radiotracers. We describe the pipeline method to assemble baseline data from various cohorts and qualitatively assessed all the data using signal-to-noise and contrast-to-noise ratios as well as the median of intensity. The database is stored and available through the PRIME-DE consortium repository.

scientific communication and education↗

bioRxiv2022

Virtual histology of Alzheimer's Disease: why are amyloid-β plaques visible with X-ray phase-contrast imaging?

Amyloid-{beta} (A{beta}) plaques from Alzheimers Disease (AD) can be visualized ex vivo in label-free brain samples using synchrotron X-ray phase-contrast tomography (XPCT). However, for XPCT to be useful as a screening method for amyloid pathology, it is essential to understand which factors drive the detection of A{beta} plaques. The current study was designed to test the hypothesis that A{beta}-related contrast in XPCT could be caused by the A{beta} fibrils and/or by metals trapped in the plaques. This study probed the fibrillar and elemental compositions of A{beta} plaques in brain samples from different types of AD patients and AD models to establish a relationship between XPCT contrast and A{beta} plaque characteristics. XPCT, micro-Fourier-Transform Infrared spectroscopy and micro-X-Ray Fluorescence spectroscopy were conducted on human samples (genetic and sporadic cases) and on four transgenic rodent strains (mouse: APPPS1, ArcA{beta}, J20; rat: TgF344). A{beta} plaques from the genetic AD patient were visible using XPCT, and had higher {beta}-sheet content and higher metal levels than the sporadic AD patient, which remained undetected by XPCT. A{beta} plaques in J20 mice and TgF344 rats appeared hyperintense on XPCT images, while they were hypointense with an hyperintense core in the case of APPPS1 and ArcA{beta} mice. In all four transgenic strains, {beta}-sheet content was similar, while metal levels were highly variable: J20 (zinc and iron) and TgF344 (copper) strains showed greater metal accumulation than APPPS1 and ArcA{beta} mice. Hence, a positive contrast formation of A{beta} plaques in XPCT images appeared driven by biometal entrapment. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/509706v2_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@56e672org.highwire.dtl.DTLVardef@1336d85org.highwire.dtl.DTLVardef@15b6690org.highwire.dtl.DTLVardef@1aaa6cb_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIAmyloid-{beta} plaques in the different forms of Alzheimers Disease have various contrasts in X-ray phase-contrast tomography C_LIO_LIIn transgenic rodents, a core-restricted, positive contrast is driven by the level of metal entrapment within plaques C_LIO_LIIn humans, greater and more diffuse metal accumulation lead to a positive contrast in a genetic case of AD C_LI

biophysics↗

bioRxiv2021

Brain virtual histology with X-ray phase-contrast tomography Part I: whole-brain myelin mapping in white-matter injury models

White-matter injury leads to severe functional loss in many neurological diseases. Myelin staining on histological samples is the most common technique to investigate white-matter fibers. However, tissue processing and sectioning may affect the reliability of 3D volumetric assessments. The purpose of this study was to propose an approach that enables myelin fibers to be mapped in the whole rodent brain with microscopic resolution and without the need for strenuous staining. With this aim, we coupled inline (propagation-based) X-ray phase-contrast tomography (XPCT) to ethanol-induced brain sample dehydration. We here provide the proof-of-concept that this approach enhances myelinated axons in rodent and human brain tissue. In addition, we demonstrated that white-matter injuries could be detected and quantified with this approach, using three animal models: ischemic stroke, premature birth and multiple sclerosis. Furthermore, in analogy to diffusion tensor imaging (DTI), we retrieved fiber directions and DTI-like diffusion metrics from our XPCT data to quantitatively characterize white-matter microstructure. Finally, we showed that this non-destructive approach was compatible with subsequent complementary brain sample analysis by conventional histology. In-line XPCT might thus become a novel gold-standard for investigating white-matter injury in the intact brain. This is Part I of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part II shows how in-line XPCT enables the whole-brain 3D morphometric analysis of amyloid-{beta} (A{beta}) plaques. HighlightsO_LIX-ray phase-contrast tomography (XPCT) enables myelin mapping of the whole brain C_LIO_LIXPCT detects and quantifies white-matter injuries in a range of diseases C_LIO_LIFiber directions and anisotropy metrics can be retrieved from XPCT data C_LIO_LIXPCT is compatible with subsequent conventional histology of brain samples C_LIO_LIXPCT is a powerful virtual histology tool that requires minimal sample preparation C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/436852v3_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@1b06ba6org.highwire.dtl.DTLVardef@16b8d4aorg.highwire.dtl.DTLVardef@91cfborg.highwire.dtl.DTLVardef@4dcbca_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Brain virtual histology with X-ray phase-contrast tomography Part II: 3D morphologies of amyloid-β plaques in Alzheimer's disease models

While numerous transgenic mouse strains have been produced to model the formation of amyloid-{beta} (A{beta}) plaques in the brain, efficient methods for whole-brain 3D analysis of A{beta} deposits are lacking. Moreover, standard immunohistochemistry performed on brain slices precludes any shape analysis of A{beta} plaques. The present study shows how in-line (propagation-based) X-ray phase-contrast tomography (XPCT) combined with ethanol-induced brain sample dehydration enables hippocampus-wide detection and morphometric analysis of A{beta} plaques. Performed in three distinct Alzheimer mouse strains, the proposed workflow identified differences in signal intensity and 3D shape parameters: 3xTg displayed a different type of A{beta} plaques, with a larger volume and area, greater elongation, flatness and mean breadth, and more intense average signal than J20 and APP/PS1. As a label-free non-destructive technique, XPCT can be combined with standard immunohistochemistry. XPCT virtual histology could thus become instrumental in quantifying the 3D spreading and the morphological impact of seeding when studying prion-like properties of A{beta} aggregates in animal models of Alzheimers disease. This is Part II of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part I shows how in-line XPCT enables 3D myelin mapping in the whole rodent brain and in human autopsy brain tissue. HighlightsO_LIX-ray phase-contrast tomography (XPCT) enables whole brain detection of A{beta} plaques C_LIO_LIMorphometric parameters of A{beta} plaques may be readily retrieved from XPCT data C_LIO_LINew shape parameters were successfully extracted from three Alzheimers disease models C_LIO_LIA Fiji-based "biologist-friendly" analysis workflow is proposed and shared C_LIO_LIXPCT is a powerful virtual histology tool that requires minimal sample preparation C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/436908v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@7c3167org.highwire.dtl.DTLVardef@18f689eorg.highwire.dtl.DTLVardef@1d9c72org.highwire.dtl.DTLVardef@a027a_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

neuroscience↗