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Paralysis: neurons that restore walking have been identified

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(Vienna, 10 November 2022) In an animal model, a study, led by EPFL Lausanne with the participation of MedUni Vienna's Center for Medical Physics and Biomedical Engineering, has identified a class of neurons that provides the crucial impetus for restoring walking ability after spinal cord injuries resulting in paralysis. This study was recently published in the leading journal "Nature". Studies at the Medical University of Vienna are currently investigating whether this type of nerve cell can also be found in the human spinal cord. The first promising pilot results are already available.

The research team, led by Grégoire Courtine of EPFL Lausanne and including Karen Minassian of MedUni Vienna's Center for Medical Physics and Biomedical Engineering, focused on the underlying mechanisms of successful epidural stimulation in severe paralysis. This is the electrical stimulation of the spinal cord via implanted electrodes, which can help paraplegic patients to learn to walk independently once again through intensive training. Using special imaging techniques, the researchers discovered that after the therapy, glucose metabolism and, hence, activity in the lumbar spinal cord - the part of the spinal cord that houses the neuronal networks essential for walking - was drastically reduced, despite increased mobility. The researchers concluded that epidural stimulation had triggered neuroplastic changes in the spinal cord, which ultimately led to a more specific activation of neuronal networks important for walking.  

This hypothesis was subsequently confirmed in preclinical experiments, in which the scientists recognised the particular relevance of a specific class of neurons that is crucial for coordination during walking. When these neurons were genetically knocked out, this hardly affected walking ability in the animal model with an uninjured spinal cord. However, where spinal cord injury was present, walking could not be relearned, even with epidural stimulation and training. In contrast, when this class of neurons was directly chemogenetically stimulated, the mice with spinal cord injury were able to walk after training, even when epidural stimulation was turned off.

Still to be identified in the human spinal cord
The presence of this class of neurons in the human spinal cord has yet to be demonstrated. "The Medical University of Vienna is currently planning a study on this topic, which will be led by the Center for Medical Physics and Biomedical Engineering and the Division of Neuropathology and Neurochemistry of the Department of Neurology," says Karen Minassian. The first promising pilot results are already available. Together, these studies may contribute to a better understanding of neural motor control at the level of the spinal cord and how it changes after injury. "This knowledge will ultimately form the basis for the development of novel therapeutic approaches to help as many sufferers as possible to live more independently," says Karen Minassian, explaining the relevance of the research.

Publication: Nature
The neurons that restore walking after paralysis;
Claudia Kathe, Michael A. Skinnider, Thomas H. Hutson, Nicola Regazzi, Matthieu Gautier, Robin Demesmaeker, Salif Komi, Steven Ceto, Nicholas D. James, Newton Cho, Laetitia Baud, Katia Galan, Kaya J. E. Matson, Andreas Rowald, Kyungjin Kim, Ruijia Wang, Karen Minassian, John O. Prior, Leonie Asboth, Quentin Barraud, Stéphanie P. Lacour, Ariel J. Levine, Fabien Wagner, Jocelyne Bloch, Jordan W. Squair, Grégoire Courtine;
doi: 10.1038/s41586-022-05385-7