Vascular change and opposing effects of the angiotensin type 2 receptor in a mouse model of vascular cognitive impairment

Our aims were to assess the spatiotemporal development of brain pathology in a mouse model of chronic hypoperfusion using magnetic resonance imaging (MRI), and to test whether the renin-angiotensin system (RAS) can offer therapeutic benefit. For the first time, different patterns of cerebral blood flow alterations were observed in hypoperfused mice that ranged from an immediate and dramatic to a delayed decrease in cerebral perfusion. Diffusion tensor imaging revealed increases in several quantitative parameters in different brain regions that are indicative of white-matter degeneration; this began around 3 weeks after induction of hypoperfusion. While this model may be more variable than previously reported, neuroimaging tools represent a promising way to identify surrogate markers of pathology. Vascular remodelling was observed in hypoperfused mice, particularly in the anterior part of the Circle of Willis. While the angiotensin II receptor type 2 agonist, Compound 21 (C21), did not influence this response, it did promote expansion of the basilar artery in microcoil animals. Furthermore, C21-treated animals exhibited increased brain lymphocyte infiltration, and importantly, C21 had opposing effects on spatial reference memory in hypoperfused and sham mice. These results suggest that the RAS may have a role in vascular cognitive impairment

Study by MRI at high field of the transient cerebral ischemia in newborn rat

Le but de cette étude était de caractériser par IRM et SRM in vivo le développement à court et moyen terme des atteintes cérébrales consécutives à une ischémie expérimentale transitoire focale chez le rat nouveau né (P7). Les résultats obtenus ont montré que l’IRM à court terme permettait le suivi de l’extension des aires atteintes pendant l’ischémie et la reperfusion et que ce suivi avait un caractère prédictif en ce qui concerne le devenir futur de ces tissus. Le suivi a moyen terme a permis de mettre en évidence le développement d’une cicatrice gliale dans les aires atteintes, par imagerie pondérée T2, et les réorganisations des réseaux de fibres cérébrales, par imagerie du tenseur de diffusion dans cette cicatrice et dans des aires adjacentes homolatérales. Les protocoles d’IRM développés seront donc des outils performants pour l’évaluation de traitements thérapeutiques ayant pour cible ces deux processus.The aim of this study was to characterize by in vivo MRI and MRS the short term and middle term developments of cerebral injuries following an experimental transient focal ischemia in the newborn rat (P7). The results show the efficiency of MRI to monitor the short term extent of the injured areas during ischemia and reperfusion and to predict the extent of the middle term extent of brain damage. The middle term monitoring has shown the development of a glial scar in the injured areas, by T2 weighted imaging, and the remodeling of the cerebral fiber networks, by Diffusion Tensor Imaging both in the glial scar and in ipsilateral adjacent areas. The monitoring of cerebral ischemia by these imaging methods will be thus a useful tool to evaluate the efficiency of therapeutic treatments directed toward these two processes

Etude par IRM à haut champ de l'ischémie cérébrale transitoire chez le rat nouveau né

Le but de cette étude était de caractériser par IRM et SRM in vivo le développement à court et moyen terme des atteintes cérébrales consécutives à une ischémie expérimentale transitoire focale chez le rat nouveau né (P7). Les résultats obtenus ont montré que l IRM à court terme permettait le suivi de l extension des aires atteintes pendant l ischémie et la reperfusion et que ce suivi avait un caractère prédictif en ce qui concerne le devenir futur de ces tissus. Le suivi a moyen terme a permis de mettre en évidence le développement d une cicatrice gliale dans les aires atteintes, par imagerie pondérée T2, et les réorganisations des réseaux de fibres cérébrales, par imagerie du tenseur de diffusion dans cette cicatrice et dans des aires adjacentes homolatérales. Les protocoles d IRM développés seront donc des outils performants pour l évaluation de traitements thérapeutiques ayant pour cible ces deux processus.The aim of this study was to characterize by in vivo MRI and MRS the short term and middle term developments of cerebral injuries following an experimental transient focal ischemia in the newborn rat (P7). The results show the efficiency of MRI to monitor the short term extent of the injured areas during ischemia and reperfusion and to predict the extent of the middle term extent of brain damage. The middle term monitoring has shown the development of a glial scar in the injured areas, by T2 weighted imaging, and the remodeling of the cerebral fiber networks, by Diffusion Tensor Imaging both in the glial scar and in ipsilateral adjacent areas. The monitoring of cerebral ischemia by these imaging methods will be thus a useful tool to evaluate the efficiency of therapeutic treatments directed toward these two processes.EVRY-Bib. électronique (912289901) / SudocSudocFranceF

An MRI-SPI and NMR relaxation study of drying–hydration coupling effect on microstructure of cement-based materials at early age

International audienc

From Systemic Inflammation to Neuroinflammation: The Case of Neurolupus

It took decades to arrive at the general consensus dismissing the notion that the immune system is independent of the central nervous system. In the case of uncontrolled systemic inflammation, the relationship between the two systems is thrown off balance and results in cognitive and emotional impairment. It is specifically true for autoimmune pathologies where the central nervous system is affected as a result of systemic inflammation. Along with boosting circulating cytokine levels, systemic inflammation can lead to aberrant brain-resident immune cell activation, leakage of the blood⁻brain barrier, and the production of circulating antibodies that cross-react with brain antigens. One of the most disabling autoimmune pathologies known to have an effect on the central nervous system secondary to the systemic disease is systemic lupus erythematosus. Its neuropsychiatric expression has been extensively studied in lupus-like disease murine models that develop an autoimmunity-associated behavioral syndrome. These models are very useful for studying how the peripheral immune system and systemic inflammation can influence brain functions. In this review, we summarize the experimental data reported on murine models developing autoimmune diseases and systemic inflammation, and we explore the underlying mechanisms explaining how systemic inflammation can result in behavioral deficits, with a special focus on in vivo neuroimaging techniques

Improvement of the Off-Resonance Saturation, an MRI sequence for positive contrast with SPM particles: Theoretical and experimental study

The SuperParaMagnetic particles (SPM particles) are used as contrast agents in MRI and produce negative contrast with conventional T2 or T2(∗)-weighted sequences. Unfortunately, the SPM particle detection on images acquired with such sequences is sometimes difficult because negative contrast can be created by artifacts such as air bubbles or calcification. To overcome this problem, new sequences as Off-Resonance Saturation (ORS) were developed to produce positive contrast with SPM particles. This work explores a new way to optimize the contrast generated by the ORS sequence by increasing the number of saturation pulses applied before the imaging sequence. This modified sequence is studied with numerical simulations and experiments on agarose gel phantoms. A theoretical model able to predict the contrast for different values of the sequence parameters is also developed. The results show that the contrast increases with the saturation pulses number with an optimal value of three saturation pulses in order to avoid artifacts and limit the Specific Absorption Rate (SAR) effect. The dependence of the contrast on the SPM particle concentration and sequence parameters is comparable to what was observed for the ORS sequence

White matter reorganization and functional response after focal cerebral ischemia in the rat.

After stroke, the brain has shown to be able to achieve spontaneous functional recovery despite severe cerebral damage. This phenomenon is poorly understood. To address this issue, focal transient ischemia was induced by 60 min middle cerebral artery occlusion in Wistar rats. The evolution of stroke was followed using two magnetic resonance imaging modalities: diffusion spectrum imaging (acquired before, one and four weeks after stroke) and functional magnetic resonance imaging (acquired before and five weeks after stroke). To confirm the imaging observations, immunohistochemical staining for myelin, astrocytes and macrophages/microglia was added. At four weeks after stroke, a focal alteration of the diffusion anisotropy was observed between the ipsilesional ventricle and the lesion area. Using tractography this perturbation was identified as reorganization of the ipsilesional internal capsule. Functional imaging at five weeks after ischemia demonstrated activation of the primary sensorimotor cortex in both hemispheres in all rats except one animal lacking a functional response in the ipsilesional cortex. Furthermore, fiber tracking showed a transhemispheric fiber connection through the corpus callosum, which-in the rat without functional recovery-was lost. Our study shows the influence of the internal capsule reorganization, combined with inter-hemispheric connections though the corpus callosum, on the functional activation of the brain from stroke. In conclusion, tractography opens a new door to non-invasively investigate the structural correlates of lack of functional recovery after stroke

Bottom-up study of the MRI positive contrast created by the Off-Resonance Saturation sequence

Superparamagnetic iron oxide nanoparticles (SPM particles) are used in MRI to highlight regions such as tumors through negative contrast. Unfortunately, sources as air bubbles or tissues interfaces also lead to negative contrast, which complicates the image interpretation. New MRI sequences creating positive contrast in the particle surrounding, such as the Off-Resonance Saturation sequence (ORS), have thus been developed. However, a theoretical study of the ORS sequence is still lacking, which hampers the optimization of this sequence. For this reason, this work provides a self-consistent analytical expression able to predict the dependence of the contrast on the sequence parameters and the SPM particles properties. This expression was validated by numerical simulations and experiments on agarose gel phantoms on a 11.7 T scanner system. It provides a fundamental understanding of the mechanisms leading to positive contrast, which could allow the improvement of the sequence for future in vivo applications. The influence of the SPM particle relaxivities, the SPM particle concentration, the echo time and the saturation pulse parameters on the contrast were investigated. The best contrast was achieved with SPM particles possessing the smallest transverse relaxivity, an optimal particle concentration and for low echo times

Analysis of the modifications of MRI signal of the brachial plexus of rats: Comparative study before and after freezing/thawing.

The aim of this study was to compare the MRI signal of the brachial plexus and surrounding muscles before and after freezing/thawing on a murine model. A first MRI going through the brachial plexuses of 5 healthy Wistar rats was performed immediately post-mortem. A second MRI was performed after freezing at -30°C and then thawing at 20°C for 24hours. All MRI images were segmented to make nerve and muscular structures appear and calculate the average intensity of the MRI signal using the program ImageJ. The average nerve and muscular MRI signals were compared before and after freezing/thawing and rated in grayscale units between 0 and 255. The average intensity of the MRI signal of nerve structures was 40.315 grayscale units before freezing and 31.943 after freezing/thawing. The average intensity of the MRI signal of muscular structures was 25.44 grayscale units before freezing and 35.710 after freezing/thawing. Our results have shown that the intensity of the MRI signal of the brachial plexus was higher before freezing/thawing. The intensity of the MRI signal of muscles was lower than the intensity of the brachial plexus before freezing/thawing and higher after freezing/thawing in muscles than in brachial plexus. The MRI could be used in clinical practice to monitor the reinnervation after frozen nerve allografts

Comparison of active, passive and magnetic targeting to tumors of multifunctional paclitaxel/SPIO-loaded nanoparticles for tumor imaging and therapy

Multifunctional nanoparticles combining therapy and imaging have the potential to improve cancer treatment by allowing personalized therapy. Herein, we aimed to compare in vivo different strategies in terms of targeting capabilities: (1) passive targeting via the EPR effect, (2) active targeting of αvβ3 integrin via RGD grafting, (3) magnetic targeting via a magnet placed on the tumor and (4) the combination of magnetic targeting and active targeting of αvβ3 integrin. For a translational approach, PLGA-based nanoparticles loaded with paclitaxel and superparamagnetic iron oxides were used. Electron Spin Resonance spectroscopy and Magnetic Resonance Imaging (MRI) were used to both quantify and visualize the accumulation of multifunctional nanoparticles into the tumors. We demonstrate that compared to untargeted or single targeted nanoparticles, the combination of both active strategy and magnetic targeting drastically enhanced (i) nanoparticle accumulation into the tumor tissue with an 8-fold increase compared to passive targeting (1.12% and 0.135% of the injected dose, respectively), (ii) contrast in MRI (imaging purpose) and (iii) anti-cancer efficacy with a median survival time of 22days compared to 13 for the passive targeting (therapeutic purpose). Double targeting of nanoparticles to tumors by different mechanisms could be a promising translational approach for the management of therapeutic treatment and personalized therapy