Researchers have just identified the neurons which, activated by electrical stimulation of the spinal cord, enabled nine paralyzed patients to walk again. The resulting molecular mapping could make it possible to target neurons damaged by spinal cord lesions.
To walk, we need neurons located in the lumbar spinal cord, which are activated in a downward cascade from the brainstem. A severe spinal cord injury can then disrupt this crucial connection between the brain and the networks of nerve cells in the lower part of the spine. The consequence of the injury is permanent paralysis.
In 2018, neuroscientists showed that a technique known as ‘epidural electrical stimulation’ (SEE) could reactivate non-functioning neurons in the lumbar spinal cord right away, allowing paralyzed people to walk again, in combination with intensive training. However, the biological principles by which SEE remodels the spinal cord to restore walking remained unclear.
Electrical stimulation that restores walking
A team of researchers from the NeuroRestore center in Switzerland reports today in Nature that this same type of electrical stimulation restored walking and improved the neurological status of nine people with severe spinal cord injury. In a first human clinical trial, the nine participants (three of whom were completely paralyzed and had no sensation in their legs) participated in training in addition to receiving electrostimulation delivered by devices implanted in their spine.
This gait recovery suggests that stimulation triggers remodeling of spinal neurons. Yet, by taking a closer look at spinal cord activity in a rodent model, the researchers made a startling discovery. ” Recovery involved a reduction in neuronal activity in the lumbar spinal cord during walking. We hypothesized that this unexpected reduction reflects the activity-dependent selection of specific neuronal subpopulations that become essential for a patient to be able to walk after spinal cord injury. “, they write.
Neurons specialized in recovery
In samples of mouse spinal tissue, neuroscientists measured the genetic activity of thousands of individual neurons to obtain a detailed molecular map of walking. They then used a machine learning algorithm to search for mouse neurons that exhibited changes in gene activity, similar to those seen in walking rehabilitation in humans. The precision of this atlas shows that stimulation of the spinal cord activates a specific type of neuron: Vsx2 neurons, which are not called upon for walking in people with no lesions.
To make sure of the discovery, the team inactivated these particular neurons. ” In mice suffering from a lesion, this inactivation of Vsx2 neurons immediately stopped walking, whereas it had no effect on healthy mice. This indicates that Vsx2 neurons are both necessary and sufficient for the electrostimulation treatment to be effective and result in the reorganization of the nervous system. », indicates a press release.
The creation of this molecular atlas is an important advance that would allow neuroscientists to directly manipulate the activity of specific neurons with other treatments, such as gene therapy. According to neurologist Marc Ruitenberg, stem cell therapies could eventually replace damaged neurons in spinal cord injuries.