Shock waves promote spinal cord repair via TLR3

JCI Insight. 2020 Aug 6;5(15):e134552. doi: 10.1172/jci.insight.134552.

Abstract

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. Both SWT and TLR3 stimulation enhanced neuronal sprouting and improved neuronal survival, even in human spinal cord cultures. We identified tlr3 as crucial enhancer of spinal cord regeneration in zebrafish. Our findings indicate that TLR3 signaling is involved in neuroprotection and spinal cord repair and suggest that TLR3 stimulation via SWT could become a potent regenerative treatment option.

Keywords: Inflammation; Medical devices; Neurological disorders; Neuroscience; Surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Extracorporeal Shockwave Therapy / methods*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity
  • Neovascularization, Physiologic*
  • Neurons / cytology*
  • Neurons / metabolism
  • Neuroprotective Agents*
  • Spinal Cord Injuries / etiology
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / therapy*
  • Spinal Cord Regeneration*
  • Toll-Like Receptor 3 / physiology*
  • Zebrafish

Substances

  • Neuroprotective Agents
  • Toll-Like Receptor 3

Grant support

This work was supported by an AUVA unrestricted research grant to JH, and CT and an Austrian Science Fund (FWF) F4414 to NS.