To walk, the brain transmits commands downstream pathways that cascade from the brainstem to fire these neurons. (CREDIT: Creative Commons)
The neurons responsible for walking are located in the lumbar region of the spinal cord. To walk, the brain transmits commands downstream pathways that cascade from the brainstem to fire these neurons. Severe spinal cord injury (SCI) destroys this finely organized communication system. While the neurons located in the lumbar spinal cord are not directly damaged by trauma, the depletion of major supraspinal commands renders them non-functional. The result is permanent paralysis.
Separate case studies have reported that EES can immediately reactivate non-functioning neurons in the lumbar spinal cord, allowing people with paralysis to walk. The use of EES during neurorehabilitation (EESREHAB) further improved gait recovery, even when stimulation was turned off.
A new study by scientists at the .NeuroRestore Research Center has identified the type of neuron that is activated and remodeled when the spinal cord is stimulated, allowing patients to stand up, walk and regenerate their muscles, thereby improving their quality of life. This discovery, made in nine patients, marks a fundamental clinical breakthrough. The study was published today in the journal Nature.
As part of a multi-year research program coordinated by the two directors of .NeuroRestore – Grégoire Curtin, professor of neurology at EPFL, and Jocelyn Bloch, neurosurgeon at the University Hospital of Lausanne (CHUV), patients who were paralyzed as a result of spinal cord injury and who underwent targeted epidural electrical stimulation of the area that controls the movement of the legs, were able to restore some motor functions.
The new study not only demonstrated the effectiveness of this therapy in nine patients, but also showed that the improvement in motor function is maintained in patients after the completion of the neurorehabilitation process and the removal of electrical stimulation.
This indicated that the nerve fibers used for walking had reorganized. Scientists believe it is critical to understand exactly how this reorganization of neurons occurs in order to develop more effective treatments and improve the lives of as many patients as possible.
Vsx2 neurons reorganize to restore walking
To come to this understanding, the research team first studied the underlying mechanisms in mice. This revealed a surprising feature of the Vsx2 family of neurons: while healthy mice do not need these neurons to walk, they are required to restore motor function after spinal cord injury.
This discovery was the culmination of several stages of fundamental research. For the first time, scientists have been able to visualize the activity of a patient’s spinal cord while walking.
This led to an unexpected conclusion: in the process of stimulation of the spinal cord, the activity of neurons did decrease during walking. The scientists hypothesized that this was because neuronal activity was selectively directed towards restoring motor function.
To test their hypothesis, the research team developed an advanced molecular technology. “We created the first 3D molecular mapping of the spinal cord,” Cortin says. “Our model allows us to observe the recovery process in greater detail – at the level of neurons.”
Through their highly accurate model, the scientists found that spinal cord stimulation activates Vsx2 neurons and that these neurons become increasingly important as the reorganization process unfolds.
Implantable platform for real-time control of epidural electrical stimulation. (CREDIT: EPFL)
Universal Spinal Implant
Stephanie Lacour, a fellow EPFL professor, helped the research team confirm their findings with epidural implants developed in her lab.
Lacour adapted the implants by adding light emitting diodes that allowed the system not only to stimulate the spinal cord, but also deactivate only the Vsx2 neurons through an optogenetic process. When the system was used on mice with spinal cord injury, the mice immediately stopped walking due to neuronal deactivation, but there was no effect on healthy mice.
Sequencing of single-nuclear RNA of the lumbar spinal cord. (CREDIT: EPFL)
This means that Vsx2 neurons are both necessary and sufficient for spinal cord stimulation therapy to be effective and lead to neural reorganization.
“It’s important for neuroscientists to be able to understand the specific role that each subset of neurons plays in an activity as complex as walking,” says Bloch. “Our new study, in which nine patients in clinical trials were able to regain some degree of motor function with our implants, provides us with valuable insights into the process of reorganization of neurons in the spinal cord.”
Jordan Squire, who specializes in regenerative therapies at .Neurorestore, adds: “This paves the way for more targeted treatment of paralyzed patients. We can now aim to manipulate these neurons to regenerate the spinal cord.”
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