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This article is the original of Translational Medicine Network, please indicate the source for reprinting
Written by Jevin
Spinal cord injuries can be debilitating because they disrupt signals from the brain to the lower extremities, leading to partial or complete paralysis
.
But a recent development suggests that epidural electrical stimulation is expected to help patients regain some mobility
.
Recently, the research team of the Swiss Federal Institute of Technology published a research paper in Nature, which revealed the neurobiological mechanism
behind this therapeutic progression.
The researchers mapped a detailed molecular profile of mice with spinal cord injury as they recovered from paralysis, and then used this molecular map to identify a cell type
that was critical to spinal cord injury exercise recovery.
Cells
that play a key role in the recovery of spinal cord injury movements were finally identified.
style="box-sizing: border-box;">clinical trial
01
The research team conducted a clinical trial in which electrical stimulation therapy was administered to 9 patients with severe or complete paralysis, and 3 of the participants, all of whom were completely paralyzed, received the newly designed EES treatment
.
During EES stimulation, all patients immediately regained partial walking
ability with robotic support.
After five months of recovery from EES treatment, most of the injured people also experienced a considerable improvement in their weight-bearing capacity and continued improvement in their ability to walk
.
However, it is unclear how EES treatment leads to neural circuit reorganization so that undamaged neurons can help restore movement
.
Understanding how EES reshapes spinal cord circuits could help researchers develop more targeted techniques to help injured people regain walking and potentially enable them to return to more complex movements
.
Vsx2 neurons reorganize to resume walking
02
In addition, the research team developed a machine learning method to analyze gene expression data to identify cell types
that respond to biological stimuli.
They used this tool to pinpoint a specific type of excitatory neuron
in the lumbar spinal cord.
To determine whether such neurons promoted the restoration of the ability to walk, the researchers conducted a series of experiments in mice to examine the effects of
silencing or activating these cells.
They found that after spinal cord injury, silencing these neurons impaired EES-mediated walking recovery, while activating these neurons (even without EES treatment) improved walking
in mice.
That is, if given the appropriate stimulation and combined with motor rehabilitation, certain types of spinal cord neurons can still be "reawakened" after injury, even if they lose signal input from the brain, and their reuse will help restore the injured person's motor capacity
.
This finding represents the first time that scientists have been able to visualize the movement
of a patient's spinal cord while walking.
During spinal cord stimulation, neuronal activity is actually reduced
during walking.
3D molecular mapping of the spinal cord
03
The scientists hypothesized that this was because neuronal activity selectively pointed to restoring motor function
.
To test their hypothesis, the team developed advanced molecular techniques
.
They established the first 3D molecular mapping of the spinal cord, allowing the recovery process
to be observed at an enhanced granularity at the neuronal level.
Thanks to their highly accurate model, the scientists found that spinal cord stimulation activates Vsx2 neurons, which become increasingly important
as the reorganization process unfolds.
In addition, there is another core problem
upstream of these neurons.
Spinal cord injuries often disrupt some of the nerve pathways from the brain to the spinal cord, causing the way they are connected to each other to reorganize
.
If EES treatment alters the signals received by V2a neurons from the brain, then identifying and regulating these descending pathways may also provide another pathway
for motor recovery therapy.
The research team, from PET studies in clinical humans to preclinical mouse studies, demonstrated the critical role of such neurons in regaining the ability to walk after paralysis, and the method of analyzing cell types that respond preferentially to biological disturbances and their spatial distribution characteristics can help identify key neurons
that mediate complex behavior.
Although many challenges remain, the detailed molecular mapping and sequencing methods established by the research team will serve as a valuable research resource to guide the study
of fundamental circuits for future motion recovery.
The development of methodologies to accelerate neurological recovery, as well as the establishment of new tools for controlling specific cell types in the nervous system, will allow targeted and neural circuit-based therapies
for spinal cord injuries.
Show a brighter outlook
.
Resources:
style="white-space: normal;box-sizing: border-box;">Note: This article is intended to introduce the progress of medical research and cannot be used as a reference
for treatment options.
If you need health guidance, please go to a regular hospital
.
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