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Identification of nerve cells that restore walking after spinal cord injury

klimasbrainblog

Spinal cord injury can result in severe limitations to mobility and sensory perception. Although full recovery is often not possible, studies have shown that electrical spinal cord stimulation can achieve significant improvements in movement during rehabilitation, even in individuals with complete paralysis. In a study published in the journal Nature in 2022, Claudia Kathe and co-authors from Lausanne explored the neural basis of such improvements. They provided a detailed molecular map of the injured spinal cord in mice and identified cell types that play a central role in rehabilitation.


Originally developed over 50 years ago for pain relief, epidural electrostimulation (EES) uses flexible electrodes placed over the outer layer of the spinal cord (the dura) to activate nearby neural pathways. This method is also used to stimulate remaining nerve cells after an injury to improve motor function. Despite initial challenges in generating stimulation patterns and electrode design, significant progress has been made in this area over the last decade. Advanced electrode designs can now more specifically stimulate dorsal root regions of the spinal cord that are crucial for sensory information transmission. In one clinical trial, nine severely paralysed individuals received EES, and all showed immediate recovery of walking with robotic training during stimulation, and sustained improvement at five months.


To explore how different cell types might be involved in EES-mediated recovery, the authors developed a mouse model that recapitulates many key features of EES neurorehabilitation in humans. They then sequenced RNA from individual cells and spinal cord sections to create high-resolution maps of gene expression across multiple stages of rehabilitation. This strategy allowed them to capture detailed changes in mRNA levels that occur during EES-mediated recovery. The group had previously developed a machine learning approach to analyse gene expression data that allowed the identification of the cell types responding to a biological stimulus. They were able to show that the activation of certain neuron types by EES, such as the so-called SCVsx2::Hoxa10 neurons in the lumbar spinal cord, can lead to a reorganisation of the spinal circuits that support motor function.


Taken together, the results underscore the role of certain spinal neurons in restoring movement after injury, particularly when combined with appropriate stimulation and rehabilitation. The findings of Kathe et al. provide deep insight into the cellular and molecular processes underlying EES-mediated rehabilitation and open up new possibilities for targeted therapies for spinal cord injuries.


Reference:


Kathe C, Skinnider MA, Hutson TH, …, Bloch J, Squair JW, Courtine G (2022) The neurons that restore walking after paralysis. Nature 611:540


Image credit: Fig. 1a from Kathe et al. (2022) Nature 611:540

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