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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering

Non-invasive electrical stimulation of the cervical spinal cord to facilitate arm and hand functional re plasticity after spinal cord injury

Alternative title: Målrettet manipulasjon av perinevronale nett i spesifikke nervecelletyper: Eksperimentelle studier av adaptiv plastisitet ved ryggmargsskade

Awarded: NOK 4.7 mill.

Spinal cord injury typically causes permanent loss of sensory and motor functions. But some limited functional recovery can occur through a process called adaptive plasticity, and much current research is focused on how to promote this. In this project, we are focusing on adaptive plasticity in the circuits controlling arm and hand function, which is one of the key functional losses experienced by patients with cervical spinal cord injury. To address this, we are using mice that are trained in "reach-and-grasp" behavior, and investigating how much function they can regain after a cervical spinal cord injury. Further, we will determine whether electrical stimulation of the spinal cord after such an injury improves functional recovery. During this project, we have established training of mice in reach-and-grasp behavior, testing of that behavior using high-speed video kinematics, established methods for generating an injury to one side of the cervical spinal cord, generated such injuries in the trained mice, and established methods for tracing synaptic connections from the brain to the neurons in the spinal cord that are involved in reach-and-grasp behavior. We have made the first anatomical mapping of motoneurons that innervate grip muscles, and we now have a large amount of material documenting changes in synaptic connections after spinal cord injury. On the basis of these results, we are now working on 2 scientific articles, as well as a continuation of the project together with collaborators at the University of Barcelona.

The aim of the present proposal is to obtain proof of concept that transcutaneous cervical electrical stimulation modulates cervical spinal networks to facilitate arm and hand function recovery in cervical spinal cord injured patients. This aim will be reached by employing rodent and primate animal models to decipher molecular, cellular and physiological mechanisms that drive stimulation-induced neuromodulation and recovery, and by translating this knowledge to human experiments. This bottom to top approach employing animal models and human testing will determine the degree to which non-invasive neuromodulation of the cervical spinal cord can facilitate functional recovery of the arm and hand through enhanced transmission within the residual brain-to-spinal cord connectome. The proposal establishes a consortium with a unique combination of methodological approaches to tackle specific objectives. The human and animal experiments will be run in parallel, with results from experiments exploiting the advantages of each animal species feeding directly into clinical testing with humans. To facilitate the comparison and implementation of the results obtained, the proposal includes sharing and transfering expertise and technology between the laboratories. Stimulation protocols will be designed by Newcastle University (UK), protocols for training rodents (rats and mice) to reach and grasp will be implement by the UAB (Spain), and advanced connectome tools will be employed by the University of Oslo (Norway) to identify circuit elements involved in network plasticity, and clinical testing will be performed at Guttman Rehabilitation Hospital (Spain). Students from each laboratory will engage in training at one of the other consortium laboratories to enhance the integration of specific techniques needed to implement the WPs.

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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering