Spinal cord injury

Summary

A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. Symptoms may include loss of muscle function, sensation, or autonomic function in the parts of the body served by the spinal cord below the level of the injury. Injury can occur at any level of the spinal cord and can be complete, with a total loss of sensation and muscle function at lower sacral segments, or incomplete, meaning some nervous signals are able to travel past the injured area of the cord up to the Sacral S4-5 spinal cord segments. Depending on the location and severity of damage, the symptoms vary, from numbness to paralysis, including bowel or bladder incontinence. Long term outcomes also range widely, from full recovery to permanent tetraplegia (also called quadriplegia) or paraplegia. Complications can include muscle atrophy, loss of voluntary motor control, spasticity, pressure sores, infections, and breathing problems. In the majority of cases the da

Official source

https://en.wikipedia.org/wiki/Spinal_cord_injury

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ErbB receptor signaling directly controls oligodendrocyte progenitor cell transformation and spontaneous remyelination after spinal cord injury

Nicholas David James

We recently discovered a novel role for neuregulin-1 (Nrg1) signaling in mediating spontaneous regenerative processes and functional repair after spinal cord injury (SCI). We revealed that Nrg1 is the molecular signal responsible for spontaneous functional remyelination of dorsal column axons by peripheral nervous system (PNS)-like Schwann cells after SCI. Here, we investigate whether Nrg1/ErbB signaling controls the unusual transformation of centrally derived progenitor cells into these functional myelinating Schwann cells after SCI using a fate-mapping/lineage tracing approach. Specific ablation of Nrg1-ErbB receptors in central platelet-derived growth factor receptor alpha (PDGFR)-derived lineage cells (using PDGFRCreERT2/Tomato-red reporter mice crossed with ErbB3fl/fl/ErbB4fl/fl mice) led to a dramatic reduction in P0-positive remyelination in the dorsal columns following spinal contusion injury. Central myelination, assessed by Olig2 and proteolipid protein expression, was unchanged. Loss of ErbB signaling in PDGFR lineage cells also significantly impacted the degree of spontaneous locomotor recovery after SCI, particularly in tests dependent on proprioception. These data have important implications, namely (a) cells from the PDGFR-expressing progenitor lineage (which are presumably oligodendrocyte progenitor cells, OPCs) can differentiate into remyelinating PNS-like Schwann cells after traumatic SCI, (b) this process is controlled by ErbB tyrosine kinase signaling, and (c) this endogenous repair mechanism has significant consequences for functional recovery after SCI. Thus, ErbB tyrosine kinase receptor signaling directly controls the transformation of OPCs from the PDGFR-expressing lineage into PNS-like functional remyelinating Schwann cells after SCI.

2019

Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons

Grégoire Courtine, Yi Ding, Claudia Kathe, Jordan Squair

After spinal cord injury, tissue distal to the lesion contains undamaged cells that could support or augment recovery. Targeting these cells requires a clearer understanding of their injury responses and capacity for repair. Here, we use single nucleus RNA sequencing to profile how each cell type in the lumbar spinal cord changes after a thoracic injury in mice. We present an atlas of these dynamic responses across dozens of cell types in the acute, subacute, and chronically injured spinal cord. Using this resource, we find rare spinal neurons that express a signature of regeneration in response to injury, including a major population that represent spinocerebellar projection neurons. We characterize these cells anatomically and observed axonal sparing, outgrowth, and remodeling in the spinal cord and cerebellum. Together, this work provides a key resource for studying cellular responses to injury and uncovers the spontaneous plasticity of spinocerebellar neurons, uncovering a potential candidate for targeted therapy.

NATURE PORTFOLIO2022

Neuromodulation, the use of electrical interfaces to alter neuronal activity, has been successful as a treatment approach in several neurological disorders, including deep brain stimulation for Parkinson's disease and epidural spinal stimulation for chronic pain. Neuromodulation can also be beneficial for spinal cord injury, from assisting basic functions such as respiratory pacing and bladder control, through to restoring volitional movements and skilled hand function. Approaches range from electrical stimulation of peripheral muscles, either directly or via brain-controlled bypass devices, to stimulation of the spinal cord and brain. Limitations to widespread clinical application include durability of neuromodulation devices, affordability and accessibility of some approaches, and poor understanding of the underlying mechanisms. Efforts to overcome these challenges through advances in technology, together with pragmatic knowledge gained from clinical trials and basic research, could lead to personalised neuromodulatory interventions to meet the specific needs of individuals with spinal cord injury.

2018