Neurons that restore walking after paralysis identified

Walking: the Swiss discovery makes it easier to understand the process that occurs after paralysis. Credit: Marcos Santos/USP Images

In a multi-year research program coordinated by the two directors of .NeuroRestore – Grégoire Courtine, Professor of Neurosciences at the Ecole Polytechnique Fédérale de Lausanne (EPFL, Switzerland), and Jocelyne Bloch, Neurosurgeon at the Center Hospitalier Universitaire de Lausanne (CHUV) – , patients paralyzed by spinal cord injury who underwent targeted epidural electrical stimulation of the area that controls leg movement were able to regain some motor function.

In the new study from .NeuroRestore scientists, published in the review nature, not only was the efficacy of this therapy demonstrated in nine patients, but an improvement in motor function was demonstrated in patients after the neurorehabilitation process was completed and when electrical stimulation was turned off. This suggested that the nerve fibers used for walking had reorganized. Scientists believe that understanding exactly how this neural reorganization takes place was crucial in order to develop more effective treatments and improve the lives of as many patients as possible.

Credit: Federal Polytechnic School of Lausanne

Reorganization of neurons

To arrive at this understanding, the research team first studied the underlying mechanisms in mice. This revealed a surprising property in a family of neurons that express the Vsx2 gene: although these neurons were not required for walking in healthy mice, they were essential for the recovery of motor function after spinal cord injury. .

This discovery is the culmination of several phases of research. For the first time, scientists were able to visualize the activity of a patient’s spinal cord while walking. This led to an unexpected finding: During the process of spinal cord stimulation, neural activity actually decreased while walking. The scientists speculated that this was because neural activity was selectively directed towards recovering motor function.

To test their hypothesis, the team developed advanced molecular technology. “We established the first 3D molecular mapping of the spinal cord,” Courtine said. “Our model allows us to observe the recovery process with improved granularity – at the level of neurons.” Using their very precise model, the scientists discovered that stimulation of the spinal cord activates Vsx2 neurons and that these neurons become increasingly important as the reorganization process takes place.

versatile implant

Stéphanie Lacour, a professor at EPFL, helped the research team validate their findings with the epidural implants developed in their laboratory. Lacour adapted the implants by adding light-emitting diodes that allowed the system to not only stimulate the spinal cord, but also deactivate Vsx2 neurons on their own through an optogenetic process. When the system was used on mice with spinal cord injury, the mice immediately stopped walking due to neuron deactivation – but there was no effect on healthy mice. This implies that Vsx2 neurons are necessary and sufficient for spinal cord stimulation therapies to be effective and lead to neuronal reorganization.

“It is critical that neuroscientists be able to understand the specific role that each neuronal subpopulation plays in a complex activity like walking,” Bloch said. “Our new study, in which nine patients in the clinical trial were able to recover some degree of motor function with our implants, gives us valuable insight into the process of reorganization of neurons in the spinal cord.”

Jordan Squair, who focuses on regenerative therapies at .Neurorestore, added: “This paves the way for more targeted treatments for paralyzed patients. Now we can try to manipulate these neurons to regenerate the spinal cord.

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