Translational research

Résumé

Translational research (also called translation research, translational science, or, when the context is clear, simply translation) is research aimed at translating (converting) results in basic research into results that directly benefit humans. The term is used in science and technology, especially in biology and medical science. As such, translational research forms a subset of applied research. The term has been used most commonly in life-sciences and biotechnology but applies across the spectrum of science and humanities. In the context of biomedicine, translational research is also known as bench to bedside. In the field of education, it is defined as research which translates concepts to classroom practice. Critics of translational medical research (to the exclusion of more basic research) point to examples of important drugs that arose from fortuitous discoveries in the course of basic research such as penicillin and benzodiazepines. Other problems have stemmed from the wides

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https://en.wikipedia.org/wiki/Translational_research

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La recherche médicale se divise en recherche fondamentale et clinique. La recherche médicale fondamentale vise à mieux comprendre le corps humain et ses maladies. La recherche médicale clinique se b

La culture cellulaire est un ensemble de techniques de biologie utilisées pour faire croître des cellules hors de leur organisme (ex-vivo) ou de leur milieu d'origine, dans un but d'expérimentation sc

En médecine, un traitement, appelé aussi traitement médical, traitement thérapeutique, thérapie ou plus généralement thérapeutique, est un ensemble de mesures appliquées par un professionnel de la s

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Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury

Grégoire Courtine, Michael Aaron Miller

Although axonal regeneration after CNS injury is limited, partial injury is frequently accompanied by extensive functional recovery. To investigate mechanisms underlying spontaneous recovery after incomplete spinal cord injury, we administered C7 spinal cord hemisections to adult rhesus monkeys and analyzed behavioral, electrophysiological and anatomical adaptations. We found marked spontaneous plasticity of corticospinal projections, with reconstitution of fully 60% of pre-lesion axon density arising from sprouting of spinal cord midline-crossing axons. This extensive anatomical recovery was associated with improvement in coordinated muscle recruitment, hand function and locomotion. These findings identify what may be the most extensive natural recovery of mammalian axonal projections after nervous system injury observed to date, highlighting an important role for primate models in translational disease research.

2010

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Spinal cord injury (SCI) disrupts many essential sensorimotor and autonomic functions. Consequently, individuals with SCI can face decades with permanent disabilities. Advances in clinical management have decreased morbidity, but no clinical trial has yet demonstrated the efficacy of a repair strategy. In the past decade, Courtine lab has developed neurotechnologies that restored volitional control of locomotion in animal models of SCI. The intervention acts over two-time windows. In the short-term, the delivery of epidural electrical stimulation (EES) targeting the posterior lumbar roots with timing that mimics the natural activation of the spinal cord enables stepping in otherwise paralyzed rats. In the long-term, this targeted EES with intensive robot-assisted overground training triggers a reorganization of descending pathways that reestablished voluntary control of the paralyzed legs, even without EES. These results in animal models encouraged the transfer of these technologies and concepts to clinical applications. My contribution to this translational research program forms the core of my thesis. The first section presents a software that I developed in order to enable a comprehensive yet semi-automated analysis of kinematics and muscle activity underlying locomotor functions in humans. This toolbox allows to evaluate gait features of people with neuromotor deficits, quantify locomotor performance compared to healthy people or to monitor changes in different experimental conditions or over the time course of interventions, and automatically generate comprehensive gait reports directly understandable by scientists and clinicians. The second section introduces a paradigm shift in robotic postural assistance: the gravity-assist. We demonstrated the detrimental impact of high levels of body weight support on gravity-dependent interactions during standing and walking. We developed a gravity-assist algorithm that fine-tunes the forward and upward body weight support to reestablish these interactions based on each patientâs residual capacities. We validated the personalized gravity-assist in 30 individuals with SCI or stroke. Compared to other conditions of support, the gravity-assist enabled all the patients to improve their locomotion performance. This platform establishes refined conditions to empower and train overground locomotion in a safe yet ecological environment. The third section reports the development of targeted EES in patients with chronic SCI, and the impact of an intensive 5-month rehabilitation with gravity-assist and targeted EES on the recovery of motor functions. The key findings can be summarized as follows: We established procedures to configure targeted EES that immediately enabled voluntary control of weak or paralyzed muscles; Targeted EES boosts the residual supraspinal inputs to the lumbar spinal cord, enabling all the patients to adapt their gait to specific tasks; Locomotor performance improved during the rehabilitation; All the patients regained voluntary control over previously paralyzed muscles without EES. These combined results establish the proof-of-concept on the therapeutic potential of targeted EES and intensive, robot-assisted rehabilitation to restore locomotion after SCI. Together with similar results obtained in the US in patients with severe SCI, our findings are establishing a pathway towards the development of a viable treatment to support motor functions and improve recovery after SCI.

EPFL2019

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A versatile clearing agent for multi-modal brain imaging

Irene Costantini, Jean Pierre Ghobril, Henry Markram, Francesco Saverio Pavone, Ludovico Silvestri

Extensive mapping of neuronal connections in the central nervous system requires high-throughput mm-scale imaging of large volumes. In recent years, different approaches have been developed to overcome the limitations due to tissue light scattering. These methods are generally developed to improve the performance of a specific imaging modality, thus limiting comprehensive neuroanatomical exploration by multi-modal optical techniques. Here, we introduce a versatile brain clearing agent (2,2'-thiodiethanol; TDE) suitable for various applications and imaging techniques. TDE is cost-efficient, water-soluble and low-viscous and, more importantly, it preserves fluorescence, is compatible with immunostaining and does not cause deformations at sub-cellular level. We demonstrate the effectiveness of this method in different applications: in fixed samples by imaging a whole mouse hippocampus with serial two-photon tomography; in combination with CLARITY by reconstructing an entire mouse brain with light sheet microscopy and in translational research by imaging immunostained human dysplastic brain tissue.

Nature Publishing Group2015

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EPFL2019