The intricate coordination of neurons in the lumbar spinal cord plays a vital role in enabling walking. However, severe spinal cord injuries disrupt the communication between the brain and these neurons, resulting in permanent paralysis. In a groundbreaking study conducted by scientists at the NeuroRestore research center, a breakthrough discovery has been made, identifying the specific type of neuron activated and remodeled through spinal cord stimulation. This finding has led to the restoration of motor function, allowing paralyzed patients to stand, walk, and rebuild their muscles, significantly improving their quality of life.

Reactivating Neurons through Electrical Stimulation:

Previously, isolated case studies hinted at the potential of epidural electrical stimulation (EES) in reactivating nonfunctional neurons in the lumbar spinal cord, enabling paralyzed individuals to regain the ability to walk. The application of EES during neurorehabilitation (EESREHAB) has shown even more promising results, enhancing the recovery of walking abilities, even when the stimulation is turned off. This new study, published in Nature, expands on these findings and demonstrates the efficacy of this therapy in nine patients, with sustained motor function improvement even after the completion of the neurorehabilitation process and cessation of electrical stimulation.

Neuronal Reorganization Unveiled:

The research team, led by Grégoire Courtine, a neuroscience professor at EPFL, and Jocelyne Bloch, a neurosurgeon at Lausanne University Hospital (CHUV), embarked on a multi-year research program to understand the underlying mechanisms behind this neuronal reorganization. Their investigation began with studying mice, which unveiled a significant property within a family of neurons expressing the Vsx2 gene. While these neurons are not essential for walking in healthy mice, they play a vital role in the recovery of motor function following a spinal cord injury.

Unveiling the Reorganization Process:

For the first time, the researchers were able to visualize the spinal cord activity of a patient while walking, leading to an unexpected revelation. During spinal cord stimulation, neuronal activity decreased during walking, indicating selective direction of neuronal activity towards motor function recovery. To delve deeper, the team developed advanced molecular technology, creating a precise 3D molecular cartography of the spinal cord at the neuron level. This breakthrough allowed them to identify the activation of Vsx2 neurons through spinal cord stimulation and their increasing significance in the reorganization process.

Validating the Findings:

The research team collaborated with EPFL professor Stéphanie Lacour, who integrated light-emitting diodes into the epidural implants, enabling both spinal cord stimulation and the deactivation of Vsx2 neurons through optogenetics. Testing this system on mice with spinal cord injuries confirmed that deactivating Vsx2 neurons immediately halted walking, while healthy mice remained unaffected. This discovery solidified the understanding that Vsx2 neurons are not only necessary but also sufficient for the effectiveness of spinal cord stimulation therapies and neural reorganization.

Implications for Future Treatments:

The profound insights gained from this study have paved the way for more targeted treatments for paralyzed patients. Understanding the specific roles of each neuronal subpopulation involved in complex activities like walking is crucial. The successful recovery of motor function in nine clinical-trial patients through the use of implants provides invaluable knowledge about the reorganization process of spinal cord neurons. Jordan Squair, focusing on regenerative therapies within NeuroRestore, believes that these findings open possibilities for manipulating these neurons to regenerate the spinal cord, offering hope for further advancements in treatment options.

Conclusion:

The NeuroRestore research center’s remarkable study has unveiled the transformative potential of spinal cord stimulation in restoring walking abilities for paralyzed individuals. By identifying and remodeling specific neurons, patients have achieved significant motor function improvements, with lasting effects even after the cessation of electrical stimulation. This groundbreaking research provides critical insights into the reorganization process of spinal cord neurons, ultimately leading to more targeted and effective treatments for paralysis. With this newfound knowledge, the door is open for future breakthroughs in regenerative therapies aimed at restoring mobility and enhancing the lives of paralyzed patients.

By Impact Lab