Since its invention some thirty years ago by neurosurgeon Alim Louis Benabid, the deep brain stimulation has become one of the favorite tools of neuroscience. First to reduce the tremors caused by Parkinson, then to fight against the You can also check out our other blog posts., THE obsessive compulsive disorder (OCD) and epilepsy. More recently, this technique has been successfully tested for Rspare the brain after head injuries.
Its restorative power has once again been demonstrated for other types of nervous system trauma, including spinal cord injuries, one of the main causes of paraplegia and tetraplegia. Researchers from the Swiss Federal Institute of Technology in Lausanne (EPFL) and the University Hospital of Lausanne in Lausanne, Switzerland, have just shown that deep brain stimulation can help these paralyzed people walk again. These promising results, published on December 2, 2024, in the journal Nature Medicine.
Stimulate neurons that survive after injury
Spinal trauma damages the spinal cord and can sever its connection to the limbs, particularly the legs, causing paralysis. Often, however, this disconnection is not complete, leaving some of the nerve tissue intact. The brain can therefore continue to send commands to the legs via these remaining neurons, which can allow it to partially restore movement and therefore walking. However, this recovery is often slow and incomplete, preventing a return to a normal gait. In these cases, the goal of stimulation is to take advantage of this residual connection to increase the brain's signal to the limbs and thus improve recovery.
The hypothalamus plays a key role in restoring walking
The researchers first found the target to stimulate by making highly detailed maps of brain activity in mice before and after spinal cord injury. To do this, they measured transcriptional activity (and thus the activation of gene expression) in cells in brain regions that connect to the spinal cord (specifically, the lumbar region, below the injury). The goal was to identify which cells shut down due to the injury, but then turned back on when the body tried to walk again. The second criterion was that the density of neuronal projections from the region where these cells are located should decrease after the injury (showing that it directly impacts them), then increase and allow enough connections to be recreated to restore walking.
They thus identified the hypothalamus, a structure located at the base of the brain. And indeed, the activation of neurons in this region by optogenetics was sufficient to improve the gait of mice that had suffered these lesions. However, it was not directly the neurons originating from the hypothalamus that stimulated walking. They passed their message through neurons in the brainstem, which connects the brain and spinal cord.
Deep brain stimulation helps the spinal cord repair itself
Once the correct region was identified, the researchers tested deep brain stimulation to activate it, which had an immediate effect on the mice's gait. These results were later confirmed in rats, which can walk on both hind legs if their bodies are supported. Even those that had lost control of more than 80 μm of nerve tissue due to trauma regained walking thanks to hypothalamic stimulation. This intervention caused no visible discomfort or pain in the rodents.
The rats were treated with the stimulation for eight weeks, which improved their gait, even when the stimulation was turned off. This was because this intervention accelerated the creation of new neural connections at the site of the injury. This means that deep brain stimulation not only improved gait, but also helped the body repair itself more quickly.
Hope for people paralyzed by trauma
After validation in rodents, it was the turn of humans. The researchers used functional magnetic resonance imaging to observe the brains of 21 healthy people to precisely identify the part of the hypothalamus that was activated during walking. They then implanted electrodes stimulating this region in two people who had suffered spinal cord injuries but were able to walk a little with the help of walkers. This stimulation had immediate results, increasing muscle activity in the legs and allowing the participants to walk more easily and with less fatigue.
The participants then underwent three months of rehabilitation, with nine hours of stimulation per week. As in rodents, this regular stimulation facilitated the regeneration of neural connections in the spinal cord, partially repairing the lesion. Last year on vacation I was able to walk down a few steps and back to the sea using stimulation.", said one of the participants, Wolfgang Jager, a 54-year-old Austrian who has been in a wheelchair since 2006 after a skiing accident, in a press release.
The next step will be to combine several approaches
“ This research demonstrates that the brain plays a key role in the recovery process from paralysis, explains Gregoire Courtine, professor of neuroscience at EPFL and author of the study. Surprisingly, it is unable to take full advantage of the neuronal projections that survive after spinal cord injury. Here, we have discovered how to exploit a small region of the brain, previously unknown for its role in gait production, to engage these residual connections and improve neurological recovery in people with spinal cord injuries.
Last year, his team presented another approach to restoring walking in paralyzed people, which was based on a direct stimulation of the spinal cord below the lesion. The integration of our two approaches – brain and spinal stimulation – will offer a more comprehensive recovery strategy for patients with spinal cord injuries.", he says. However, before combining these two techniques, it will be necessary to confirm the effectiveness of deep brain stimulation in a larger number of patients. However, these initial results are extremely encouraging and could lead in the short term to a new therapeutic treatment to help paralyzed people regain their mobility.
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