Les lésions de la moelle épinière (LME) font partie des plus graves maladies du système nerveux central (SNC). Elles peuvent induire des effets physiques et psycho-sociaux dramatiques chez les patients et d’importants coûts pour le système de santé. Après une lésion, une cascade d’évènements est enclenchée perturbant les structures et populations cellulaires à proximité. Une des conséquences est la formation de la cicatrice gliale, constituée de diverses populations cellulaires telles que les formes activées de microglies et d’astrocytes. Les fibroblastes produisant du collagène sous l’action d’astrocytes participent au processus fibrotique. La cicatrice gliale constitue une dense barrière physique et chimique, aux effets à la fois bénéfiques et délétères. Aucun traitement curatif n’existe à l’heure actuelle. Cependant, des thérapies pharmaceutiques ont été développées, notamment par la déplétion transitoire de la microglie en utilisant le GW2580, un traitement qui inhibe le récepteur CSF1R impliqué dans la partie proliférative des cellules gliales.Le rôle du collagène dans la formation de la cicatrice gliale a été peu exploré comparé à ceux de la microglie et des astrocytes. Le collagène fibrillaire tel que le collagène de type I est bien connu dans les processus de cicatrisation classiques et se caractérise par une organisation supramoléculaire en fibrilles striées regroupées en une structure cylindre et finalement associées en fibres. Cet assemblage lui confère des propriétés optiques uniques pouvant être directement détectées par des mesures d’optique non-linéaire (ONL) telle que la génération de seconde harmonique (GSH) sans préparation ou un marquage de l’échantillon. De plus, la GSH est un signal cohérent dépendant de la polarisation du laser incident, et des mesures de GSH résolue en polarisation (P-GSH) peuvent déterminer l’arrangement supramoléculaire des fibres de collagène associé à la symétrie des fibrilles. L’approche globale proposée était d’exploiter le potentiel de l’ONL pour détecter et caractériser le collagène fibrillaire dans un modèle murin de LME, corrélant les informations structurales avec le comportement biomécanique du tissu, déterminé par microscopie à force atomique (MFA) en mesurant les forces appliquées lors de micro-nano indentations. Les fibres de collagène visibles grâce à leur signal en GSH ont été caractérisées via deux méthodes : le logiciel CurveAlign dédié à l’analyse des fibres de collagène dans les échantillons biologiques, et un algorithme codé au sein de l’équipe basé sur le «Fingerprint algorithm» pour une analyse plus adaptée à notre étude. Un « squelette » de fibres généré par cet algorithme a permis d’extraire des métriques pertinentes comme la densité de fibres, leur tortuosité, ainsi que leur orientation à un niveau local (calculant la variation circulaire de l’alignement local) et global (calculant l’entropie statistique). Le but de notre approche d’imagerie multimodale sans marquage était de révéler et suivre des biomarqueurs de la structure fibrotique, suivre l’élasticité de tissus de moelle épinière lésée à différent temps après lésion, et évaluer le potentiel effet d’un traitement au GW2580 à 6 semaines post lésion. Le signal GSH émis par le collagène fibrillaire a permis de l’identifier comme biomarqueur de la lésion. Une augmentation de la densité de fibres ainsi que la présence de fibres plus tortueuses ont été observées entre 1 et 6 semaines post lésion. Les mesures en P-GSH ont révélé la présence de deux types de symétrie des fibrilles (cylindrique et trigonal) à tous les temps après lésion. L’étude des propriétés nano-mécaniques a montré un durcissement notable de la zone lésée à partir d’une semaine post lésion, certainement corrélé à la formation de fibres de collagène.Ces observations indiquent la concomitance d’importantes modifications structurales et mécaniques au cours de l’évolution de la cicatrice fibrotique suite à une LME chez la souris.

Introduction The impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC). Methods To determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints. Results No global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden. Discussion These results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.

Spinal cord injury (SCI) leads to persistent neurological deficits without available curative treatment. After SCI astrocytes within the lesion vicinity become reactive, these undergo major morphological, and molecular transformations. Previously, we reported that following SCI, over 10% of resident astrocytes surrounding the lesion spontaneously transdifferentiate towards a neuronal phenotype. Moreover, this conversion is associated with an increased expression of fibroblast growth factor receptor 4 (Fgfr4), a neural stem cell marker, in astrocytes. Here, we evaluate the therapeutic potential of gene therapy upon Fgfr4 over-expression in mature astrocytes following SCI in adult mice. We found that Fgfr4 over-expression in astrocytes immediately after SCI improves motor function recovery; however, it may display sexual dimorphism. Improved functional recovery is associated with a decrease in spinal cord lesion volume and reduced glial reactivity. Cell-specific transcriptomic profiling revealed concomitant downregulation of Notch signaling, and up-regulation of neurogenic pathways in converting astrocytes. Our findings suggest that gene therapy targeting Fgfr4 over-expression in astrocytes after injury is a feasible therapeutic approach to improve recovery following traumatism of the spinal cord. Moreover, we stress that a sex-dependent response to astrocytic modulation should be considered for the development of effective translational strategies in other neurological disorders.

Gold nanoparticles are widely used in sensing, notably in colorimetry-based methods, where a color change is associated to the Surface Plasmon Resonance peak shift due to a binding event or an environment modification in the vicinity of the nanoparticles. In this work, we explore the sensitivity of the Second Harmonic response from gold nanoparticles of two different diameters as this response stems principally from the nanoparticle surface at small sizes as opposed to the whole volume of the nanoparticle at larger sizes. The origin of this response is therefore different from that involved in the colorimetric response, the latter being of volume origin. Upon addition of Glycerol to an aqueous solution of nanoparticles, Surface Plasmon Resonance peak shifts are first observed but they cannot fully explain the Second Harmonic intensity changes recorded. Hence, in order to gain further insights into the origin of the changes observed in the experimental data, polarization-resolved Second Harmonic measurements are performed. A mechanism where first a modification of the first hyperpolarizability of the nanoparticles due to the presence of glycerol occurs followed by nanoparticle aggregation is then proposed. The potential alternative use of this nonlinear optical method of Second Harmonic scattering for sensing purposes is then discussed in light of a figure of merit proposed to describe the sensing sensitivity observed.

Biomechanical characterization of a fibrinogen–blood hydrogel for human dental pulp regeneration.

Spinal cord injury is a dramatic disease leading to severe motor, sensitive and autonomic impairments. After injury the axonal regeneration is partly inhibited by the glial scar, acting as a physical and chemical barrier. The scarring process involves microglia, astrocytes and extracellular matrix components, such as collagen, con- structing the fibrotic component of the scar. To investigate the role of collagen, we used a multimodal label-free imaging approach combining multiphoton and atomic force microscopy. The second harmonic generation signal exhibited by fibrillar collagen enabled to specifically monitor it as a biomarker of the lesion. An increase in collagen density and the formation of more tortuous fibers over time after injury are observed. Nano-mechanical investigations revealed a noticeable hardening of the injured area, correlated with collagen fibers' formation. These observations indicate the concomitance of important structural and mechanical modifications during the fibrotic scar evolution.

Random granular media may exhibit characteristics more often related to ordered media. In the present work, this feature is observed in the polarized Second Harmonic Generation (SHG) response from reduced iron-doped lithium niobate (LN:Fe) powders, an effect that is not expected due to multiple scattering. Besides, this subsisting order property of the powders can be further controlled using magnetic induction to tailor the SHG response. The samples where characterized employing X-Ray Diffraction (XRD) and confocal Raman Spectroscopy. Their SHG response both in the absence and the presence of an external static magnetic field was then studied as the fundamental beam focus was translated from air into the powder. The SHG intensity polarization state was then studied as a function of the linear polarization of the fundamental beam for different fundamental beam focus depths. These results demonstrate that the SHG properties from LN:Fe powders can be modified through post-thermal treatment in a reducing atmosphere in view of photonic applications.