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    Philippe Pozzo di Borgo - Président d’honneur de l’IRME
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Accueil > La recherche > Congrès 2016

Congrès 2016

Compte-rendu

Avancées en matière de recherche dans les traumatismes médullaires

16 décembre 2016 - Paris

PDF - 1.3 Mo
Congrès IRME 2016
Book of abstracts

Communications orales

De 1984 à aujourd’hui

par Geneviève Rougon, directrice scientifique de l’IRME

En 1984, Jean Delourme, un industriel du médicament, crée l’IRME à la suite de l’accident de la route de son petitfils, victime d’une tétraplégie.
La création de cette Association a pour but de susciter et soutenir les équipes de recherche qui travaillent sur la thématique des traumatismes médullaires.
L’IRME a ainsi décidé de s’attaquer aux traumatismes résultant des accidents de la route, des accidents du travail, des agressions et des accidents causés par le sport. L’idée était de considérer que ces situations n’étaient pas inéluctables et qu’il fallait tout faire pour limiter le handicap. Ce projet était à l’époque, d’une grande audace car la recherche fondamentale et clinique était bien démunie devant de tels accidents ; les lésions observées étaient même considérées comme irréversibles. Aucune structure n’existait et la prise en charge n’était pas adaptée.
L’IRME a ainsi financé depuis plus de 30 ans des chercheurs, contribuant à une meilleure connaissance des problèmes liés à la réparation des lésions traumatiques ou neurodégénératives de la moelle épinière.
Le congrès qui nous réunit aujourd’hui vous propose de faire le point sur les grands axes de recherche avec d’éminents spécialistes de recherche fondamentale comme de recherche clinique, des chercheurs de laboratoires comme des médecins des hôpitaux, des cliniciens comme des comportementalistes, des biologistes cellulaires ou moléculaires…
Il a été décidé de faire le point sur les données les plus récentes concernant la connaissance de la moelle épinière et d’en présenter les travaux les plus originaux. Nous espérons vous apprendre beaucoup, soutenir tous ceux qui subissent ces traumatismes spinaux et confirmer les espoirs de ceux qui croient aux progrès de la recherche dans le domaine.

Modulating Neural Activity To Reshape Corticospinal System Function : From Development to Electroceuticals for Spinal Injury Repair / Modulation de l’activité neurale pour remodeler la fonction du système corticospinal : du développement aux stimulations électriques pour la réparation de la moelle épinière lésée

John (Jack) Martin
Ph.D., Professor, Neural Development & Repair Cluster Leader Department of Physiology, Pharmacology & Neuroscience, CUNY School of Medicine@CCNY,
Harris Hall - 203
160 Convent Avenue
New York, NY 10031
Laboratory : CCNY Center for Discovery and Innovation (CDI) ; 3-South

Since most spinal cord injuries are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the different pathways, the corticospinal tract (CST) is most associated with skilled motor functions. CST loss following injury leads to movement impairments and paralysis. To restore motor function after spinal cord injury will require repair of the damaged CST.
In my presentation I will discuss how our development studies identified that neural activity of the corticospinal motor system is critical for establishing specific and strong connections between the CST and spinal motor circuits. Our developmental studies have informed neural activity-based strategies for repair of the damaged CST in maturity.
I will consider how stimulation of the motor cortex in maturity activates a growth program that promotes CST axon sprouting and the formation of spinal connections. Using different motor cortex and spinal cord stimulation strategies, I will show how activity-dependent plasticity can be harnessed to help reconnect the motor cortex with spinal motor circuits and, in turn, promote recovery of skilled motor function after brain and spinal cord injury.

Neural Stem Cells and Associated Strategies for Spinal Cord Regeneration / Les cellules souches neurales et stratégies associées pour la régénération de la moelle épinière

Charles H. Tator
CM, MD, PhD, FRCSC FACS,
Professor of Neurosurgery, University of Toronto,
Division of Neurosurgery, Toronto Western Hospital,
Founder, ThinkFirst Canada. Board Member, Parachute Canada

During the past 50 years there has been a major increase in knowledge of the pathophysiology of acute SCI, and this has led to the discovery of many effective therapies in experimental models, some of which have been successfully translated to the treatment of human SCI. This talk will emphasize the transplantation of neural stem cells, with or without bioengineered scaffolds and local drug delivery strategies.
Many types of neural and non-neural cells have been used for transplantation in human SCI. Current human trials in Europe and North America involve neural stem cells as these have the best track record in experimental models for replacing lost neural tissue. However, even with neural stem cells it is unclear as to which cell is optimal. As well, there is very little known about the optimal site and interval after trauma for transplantation. Bioengineered scaffolds are also being transplanted into SCI patients, so far without cell transplants, but in experimental models combination strategies of cells and scaffolds have been tested. Many techniques have been used for local administration of pharmacological agents in fibrin glue and hydrogel matrices from subarachnoid or extradural sites. The agents delivered locally have included growth factors and transcription agents in various experimental models and some in humans with SCI.

Dormancy vs activation of the stem cell niche in spinal cord injury : gene networks and cellular diversity within the human and murine central canal cells / Dormance et réactivation de la niche de cellules souches dans les lésions médullaires : gènes et diversité cellulaire du canal central humain et murin

Jean-Philippe Hugnot
Professor
INSERM U1051
“Cerebral plasticity, Stem cells and Glial tumors” team
Institute for Neuroscience (INM)
Hôpital Saint Éloi - Montpellier

The adult spinal cord contains a pool of neural stem cells in a niche situated around the central canal. These cells, present in rodents and in man, are able to form new neuronal and glial cells in vitro. In contrast to the brain, the spinal cord niche is in a dormant state and produces no or few new cells in the normal situation. However the niche can be readily re-activated and generate new cells in spinal cord traumas. Our lab has characterized the human and mouse spinal cord niches in depth and showed that far from being a single layer of cells, the central canal region is composed of several cell types which show immaturity features and that the niche maintains the activation of several developmental signalling pathways.
We explored the molecular mechanisms underlying niche activation after injury. We used laser microdissection and microarray screening to decipher the early molecular events taking place during activation. This led us to show that the Mapk/Ras signalling is rapidly activated in the niche after injury and we identified several potential targets of this pathway which may orchestrate the activation. In order to describe further the spatial organisation of the niche we microdissected the ventral, lateral and dorsal parts of the central canal. We identified several genes which are more specific of the different regions of the niche and this enabled us to identify a new stem cell population expressing the
homeogen Msx1 and which is located in the dorsal part of the niche. To explore the conservation of the niche in mammals, the human spinal cord niche was also explored by immunohistochemistry and transcriptome analysis.

J.-P. Hugnot, B. Rothhut, C. Ripoll, D. Mamaeva, P. Guigue, H. Gazalah, F. Perrin, H. Noristani, L. Bauchet

Cell therapy to repair damaged cerebral cortex / Thérapie cellulaire pour réparer le cortex cérébral endommagé

Afsaneh Gaillard
Professor
INSERM U1084, Experimental and Clinical Neurosciences Laboratory,
Cellular Therapies in Brain Diseases group
Université de Poitiers, Poitiers

Injury to the human central nervous system (CNS) is devastating due to the poor ability of CNS to self-repair. A main goal of research in our laboratory is to identify strategies to promote neural repair in cortical injury and related neurological conditions. Neural transplantation has been assessed as a potential approach to restore brain function by replacing lost neurons with healthy new ones. We previously found that grafted foetal cortical neurons could effectively re-establish specific patterns of projections and synapses following adult cortical lesions (Gaillard et al., Nat Neurosciences 2007) indicating that cellular repair of cortical and cortical output circuitry is possible.
Embryonic stem cells constitute a promising tool for the genetic dissection of neural development and for the modelling of human diseases.
In addition, the recent advent of induced pluripotent stem cells technology, by which adult cells can be reprogrammed to embryonic stem (ES) like cells, opens realistic venues for the modelling and treatment of neural diseases.
We have previously shown that mouse and human cortical neurons derived embryonic stem cells transplanted into cortex of newborn mouse mice, established specific pattern of projections corresponding to those of endogenous cortical neurons (Gaspard et al., Nature 2008 ; Espuny-Camacho et al., Neuron, 2013). More recently, we have shown that transplantation of mouse ESC-derived neurons of appropriate cortical areal identity can contribute to the functional reconstruction of an adult damaged cortical circuit, (Michelsen et al., Neuron 2015).
A critical barrier hindering application of transplantation strategies for a wide range of traumatic injuries is the determination of a suitable time window for therapeutic intervention. Here, we have recently reported that a one-week delay between the lesion and transplantation significantly enhances graft vascularization, survival and proliferation of grafted cells. More importantly, the delay dramatically increases the density of projections developed by grafted neurons and improves functional repair and recovery as assessed by intravital dynamic imaging and behavioral tests.
These findings open new avenues in cell transplantation strategies as they indicate successful brain repair may occur following delayed transplantation.

Regenerative biomaterial matrices for traumatic spinal cord repair / Matrice régénérative à base de biomatériau pour la réparation de la moelle épinière traumatique

Fatiha Nothias
PhD, CNRS Research Director
Team Leader : “Axon growth and regeneration”
Laboratoire Neuroscience Paris Seine
CNRS UMR 8246, Inserm U1130, Université P. & M. Curie Bat A - Paris

The ongoing search for novel, efficient therapeutic strategies for treatment of spinal cord injury (SCI) should greatly profit from the recent progress in the production of innovative biomaterials that when implanted into the lesion site, will function both as extracellular matrix substitute, and as bioactive support structure.
Accordingly and as first step, we developed a therapeutic strategy based on the use of chitosan polymer, that exhibits ideal characteristics for tissue engineering. Biological evaluation of diverse formulations (varying in physical and chemicals features) allowed determining the formulations best suited to integrate into spinal cord tissue. Our experimental paradigm is a thoracic dorsal hemisection in adult female rat, with or without implantation of polymer directly after the lesion. Indeed, implantation of the selected chitosan hydrogel formulation induces (i) strong reduction of the astrocytic reaction, (ii) functional vascularization within the implant, (iii) modulated inflammatory response (iv), and most remarkably, growth of a very high number of axons through the implant, evidence for the material per se being extremely favorable for axon regrowth. Finally, these structural remodeling is associated with an improvement of the partial locomotor recovery. Because it effectively induces neural tissue repair, the chitosan biomaterial may be a promising new approach to treat SCI.

Spinal cord investigations by multimodal MRI and multiphysics approaches / Investigations médullaires par IRM multimodale et approches multi-physiques

Virginie Callot
PhD, CNRS Research Director
Centre de Résonance Magnétique Biologique et Médicale (CRMBM-CEMEREM)
UMR 7339, CNRS, Aix-Marseille Université - Faculté de Médecine

Magnetic Resonance Imaging (MRI) plays a crucial role in evaluating and detecting spinal cord (SC) injury, and “conventional” MR techniques (T1-weighted, T2-weighted) usually bring sufficient diagnostic information. Such methods are nonetheless insufficient to fully characterize the underlying pathophysiological processes and further SC tissue impairment, hence justifying the need for multimodal MRI.
In this presentation, a short - and non-exhaustive - overview of what can be done using quantitative MRI will be given. MR methods, including diffusion, perfusion and spectroscopy, dedicated to mouse spinal cord injury exploration will be described. Multimodal MR methods dedicated to human clinical research will be presented as well, along with the latest results obtained on human whole-body ultra-high field MR system (7T). Finally, a brief overview of potentialities offered by interdisciplinary and multi-physic approaches developed within the iLab-Spine and combining MRI and biomechanics will be given as well.

Management of neuropathic pain following spinal cord injury : now and in the future / Prise en charge de la douleur neuropathique après une lésion de la moelle épinière : présent et avenir

Jean-Baptiste Thiébaut
Médecin ADJT Spécialisé, Fondation Ophtalmologique A. de Rothschild, service de neurochirurgie et unité de traitement de la douleur,
Hôpital Raymond Poincaré, AP-HP (Garches), service de rééducation neurologique

La douleur est un symptôme fréquent dont se plaignent les blessés médullaires et son impact sur la qualité de vie de ces patients est important.
De nombreux travaux, ces dernières années, ont été consacrés au classement des différentes douleurs et à l’étude de leur prévalence avec une grande hétérogénéité des résultats. Nous limiterons cette présentation aux douleurs neuropathiques provenant directement de la lésion médullaire. De nombreux patients sont encore aujourd’hui insuffisamment soulagés. L’amélioration de la démarche thérapeutique est étroitement liée aux progrès des connaissances sur les mécanismes des douleurs.
Tableau clinique : La classification des douleurs neuropathiques des blessés médullaires en douleurs lésionnelles et sous lésionnelles doit être complétée par

  • l’étude phénotypique des douleurs (spontanées ou provoquées, continues ou paroxystiques, immédiates ou secondaires)
  • la description de l’atteinte neurologique (tableau de section complète ou incomplète)
  • le bilan habituel effectué devant toute douleur chronique à la recherche de facteurs favorisants Recherche d’un « générateur » de la douleur : L’analyse de cohortes de patients présentant un même tableau clinique permet de définir différents syndromes suivant le niveau du « générateur » de la douleur
  • Niveau médullaire (syndrome de la corne postérieure de la moelle, syndrome spinothalamique…)
  • Niveau supra médullaire Traitement
  • Démarche thérapeutique usuelle des douleurs chroniques dans un cadre multidisciplinaire, prenant en compte les différents facteurs intervenant dans la douleur
  • Les traitements médicamenteux des douleurs chroniques (antidépresseurs, antiépileptiques, anti NMDA) sont utilisés en première intention, éventuellement associés à des méthodes comportementales et cognitives
  • En fonction de l’évolution, on pose l’indication d’un traitement interventionnel ciblé du « générateur » de la douleur
    • niveau médullaire : « DREZotomie », pompe pour analgésie intrathécale (baclofen…), stimulation médullaire (syndrome spinothalamique isolé)
    • niveau supra médullaire : méthodes de stimulation proposées mais faible niveau de preuve Avenir
  • Au plan diagnostique : imagerie, marqueurs de la douleur
  • Au plan thérapeutique
    • recherche de cibles cérébrales (ultrasons pulsés)
    • développement des méthodes non invasives visant à moduler la plasticité cérébrale (stimulations non invasives, méthodes de réalité virtuelle ou augmentée)

Restoration of functional hand movements in spinal cord injury and quadriplegia using brain-computer interface / Rétablir le contrôle fonctionnel de la main chez le patient tétraplégique par l’interface cerveau machine

Ali R. Rezai
MD, Director, Neurological Institute
Associate Dean of Neuroscience
Stanley D. and Joan H. Ross Chair in Neuromodulation
Professor of Neurosurgery and Neuroscience
The Ohio State University Wexner Medical Center

Introduction
Brain Computer systems connect cortical signals to assistive technology to restore lost function in paralyzed individuals. Previous work has shown that paralyzed humans are able to use NI devices to control various assistive devices such as computers, robots, exoskeletons and wheelchairs. In this study we show that neural signals recorded from primary motor cortex can be used to control functional electrical stimulation of paralyzed hand muscles thereby allowing a chronically paralyzed human to utilize his hand in functional motor tasks.
Methods
A 24-year-old male with C5 AIS-A with zone of partial preservation to C6 bilaterally underwent implantation of a 96-channel microelectrode array into the arm area of his left primary motor cortex. Neural signals were recorded while he imagined right arm and hand movements. The neural activity was decoded in real- time and used to activate forearm muscles using a custom-built neuromuscular electrical stimulation system.
Results
Utilizing this system, the participant was able to complete functional tasks relevant to daily living that he was previously unable to complete.
Objective manual muscle test strength improved from C6 to C7-C8 level, his gross grasping ability improved from C7-C8 to C8-T1 level, and his prehensile skills improved from C5 to C6 level.
Conclusions
The system presented here is the first example of an NI device used in a paralyzed human to bridge a disconnected cotricospinal tract by connecting motor cortical neural activity to muscle activation. This device offers hope for movement and independence restoration to the many patients living with paralysis.

Neurotechnologies to restore walking after spinal cord injury / Neurotechnologies pour restaurer la marche après une lésion de la moelle épinière

Grégoire Courtine
PhD, Professor, International Paraplegic Foundation Chair in Spinal Cord Repair
Center for Neuroprosthetics and Brain Mind Institute
Swiss federal institute of technology (EPFL)

Durant la dernière décennie, l’équipe menée par le Professeur Grégoire Courtine a développé une thérapie innovante qui a rétabli la marche chez des rongeurs paralysés. Cette thérapie s’articule sur deux fenêtres temporelles. À court terme, des stimulations électriques et chimiques sont délivrées au niveau de la région de la moelle épinière qui contrôle les muscles des jambes afin de réveiller ces cellules nerveuses. À long terme, un entraînement facilité par ces stimulations électrochimiques et un système robotique de nouvelle génération encourage la réorganisation des connexions nerveuses, et donc l’amélioration des capacités locomotrices. Durant cette conférence, Grégoire présentera les étapes clés du développement de cette thérapie à l’aide de vidéos et d’infographies captivantes. Il partagera également l’aventure humaine qui a jalonné ces développements, depuis les balbutiements sur des modèles rongeurs jusqu’aux premiers tests cliniques avec des personnes souffrant de paraplégie.