Using a mix of electrical stimulation and intense physiotherapy, neople with chronic spinal cord injuries have regained their ability to walk.
All suffered from severe or complete paralysis as a result of spinal cord injuries. Incredibly, the volunteers all saw improvements immediately and continued to show improvements five months later.
A recent study by researchers from the Swiss research group NeuroRestore identified the exact nerve groups stimulated by the therapy, using mice as a starting point.
The nerve cells that orchestrate walking are found in the section of the spinal cord that runs through the lower back. Injuries to our spinal cord can interrupt the brain’s chain of signals, preventing us from walking even when those specific lumbar neurons are still intact.
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Unable to receive commands, these “walking” neurons effectively become non-functional, which can lead to permanent paralysis of the legs.
Previous research has demonstrated that electrical stimulation of the spinal cord can reverse such paralysis, but how this happened was unclear. Thus, the neuroscientist Claudia Kathe of the Federal Polytechnic School of Lausanne (EPFL) and her colleagues tested a technology called epidural electrical stimulation in nine individuals, as well as in an animal model.
The spinal cord was stimulated by a surgically implanted neurotransmitter. During this time, the patients also underwent an intensive neurorehabilitation process which involved a robotic support system assisting them as they moved in multiple directions.
The patients went through five months of stimulation and rehabilitation, four to five times a week. Surprisingly, all the volunteers were then able to take steps using a walker.
To the surprise of the researchers, the recovered patients actually showed reduced neural activity in the lumbar spinal cord while walking. The team thinks this is because the activity is fine-tuned to a specific subset of neurons essential for walking.
“When you think about it, that shouldn’t come as a surprise,” Courtine told Dyani Lewis at Nature“because in the brain, when you learn a task, that’s exactly what you see – there are fewer and fewer neurons activated” as you get better at it.
So Kathe and her team modeled the process in mice and used a combination of RNA sequencing and spatial transcriptomics – a technique that allows scientists to measure and map gene activity in specific tissues – to understand what cells were doing what.
They identified a single population of previously unknown neurons that can take over after injury, found in the intermediate laminae of the lumbar spinal cord.
This tissue, composed of cells called SCVsx2::Hoxa10 neurons, do not seem necessary for walking in healthy animals, but they seem essential for recovery after spinal cord injury, because their destruction prevented the mice from recovering. Their recruitment is however dependent on the activity.
CSVsx2::Hoxa10 neurons are “uniquely positioned” to transform brainstem information into executive commands. These are then broadcast to the neurons responsible for producing walking, Kathe and colleagues explain in their paper.
It’s just one piece of a very complicated chain of messaging and receiving cells, so there’s still a lot to study.
But, “these experiments confirmed that the participation of SCVsx2::Hoxa10 neurons is a fundamental requirement for gait recovery after paralysis,” the researchers concluded.
This new understanding could eventually lead to more treatment options and could also provide a better quality of life for people with all kinds of other spinal cord injuries.
Their research has been published in Nature.
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