Shock waves promote spinal cord repair via TLR3

JCI Insight, 2020 · DOI: https://doi.org/10.1172/jci.insight.134552 · Published: August 6, 2020

Spinal Cord Injury Regenerative Medicine Orthopedics

Simple Explanation

Spinal cord injury (SCI) remains a devastating condition with poor prognosis and very limited treatment options. Affected patients are severely restricted in their daily activities. Shock wave therapy (SWT) has shown potent regenerative properties in bone fractures, wounds, and ischemic myocardium via activation of the innate immune receptor TLR3. Here, we report on the efficacy of SWT for regeneration of SCI. SWT improved motor function and decreased lesion size in WT but not Tlr3–/– mice via inhibition of neuronal degeneration and IL6-dependent recruitment and differentiation of neuronal progenitor cells.

Study Duration

10 weeks

Participants

Male 12-week-old C57BL/6 mice and TLR3-knockout mice

Evidence Level

Not specified

Key Findings

1
SWT markedly improved locomotor function in WT animals in comparison with untreated control animals, whereas SWT had no effect in Tlr3-deficient mice.
2
MRI revealed a significant reduction of lesion size 10 weeks after injury in SWT-treated WT mice compared with that in untreated controls.
3
SWT resulted in increased TLR3 expression, with associated upregulation of TRIF, IL-6, and IL-6 receptor.

Research Summary

The present study provides evidence that SWT holds significant potential as therapeutic approach for the treatment of chronic SCI and presents mechanistic insight into its mode of regeneration. At least to some extent, this may be the result of a reduction of degenerating neurons, an effect seen as early as 72 hours after treatment and persisting for 10 weeks. Both in vitro as well as in vivo data strongly suggest the involvement of TLR3 signaling in spinal cord regeneration, in line with previous findings on cardiac regeneration.

Practical Implications

Therapeutic potential for SCI

SWT holds significant potential as a therapeutic approach for the treatment of chronic SCI.

Clinical Translation

SWT is currently in routine clinical use for other indications and could therefore efficiently be directly translated to the treatment of traumatic SCI.

Underlying mechanisms elucidation

Further studies are needed to elucidate whether TLR3-mediated SWT effects are mainly attributed to one specific cell type within the spinal cord or whether they represent an interplay of different cell types.

Study Limitations

1
As the described mouse model represents a model of chronic SCI and the zebrafish model represents an acute model of injury, results cannot be directly translated.
2
Due to the invasive animal model, sample size was low in the animal experiments.
3
The main purpose behind the MRI analysis was the quantification of spinal cord lesion size. While analyzing the images, we incidentally discovered differences in bladder volumes. Therefore, we did not standardize the voiding protocol before MRI measurements.

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