Shock waves promote spinal cord repair via TLR3
Can Gollmann-Tepeköylü, … , Michael Grimm, Johannes Holfeld
Can Gollmann-Tepeköylü, … , Michael Grimm, Johannes Holfeld
Published August 6, 2020
Citation Information: JCI Insight. 2020;5(15):e134552. https://doi.org/10.1172/jci.insight.134552.
View: Text | PDF
Research Article Inflammation Neuroscience

Shock waves promote spinal cord repair via TLR3

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.

Authors

Can Gollmann-Tepeköylü, Felix Nägele, Michael Graber, Leo Pölzl, Daniela Lobenwein, Jakob Hirsch, Angela An, Regina Irschick, Bernhard Röhrs, Christian Kremser, Hubert Hackl, Rosalie Huber, Serena Venezia, David Hercher, Helga Fritsch, Nikolaos Bonaros, Nadia Stefanova, Ivan Tancevski, Dirk Meyer, Michael Grimm, Johannes Holfeld

×

Figure 6

SWT reduces apoptosis and enhances neuronal sprouting.

Options: View larger image (or click on image) Download as PowerPoint
SWT reduces apoptosis and enhances neuronal sprouting. (A) Murine DRGs w...
(A) Murine DRGs were isolated from WT and Tlr3–/– mice and assessed with in vitro assays for characterization of neuronal sprouting, metabolic activity, and apoptosis after SWT or poly(I:C) treatment. (B) XTT assay revealed improved viability of DRGs after SWT in WT but not Tlr3–/– cells. Again, poly(I:C) had no effect on DRG cultures analyzed for viability. *P < 0.05. n = 7–12. (C) DRGs were subjected to FCS starvation. SWT resulted in a significant reduction of apoptotic neurons, but only in WT cells. *P < 0.05. n = 12–15. (D) Representative images of neuronal sprouting after SWT. Scale bar: 100 μm. (E) SWT stimulated neuronal sprouting in DRGs derived from WT mice. Sprouting was not stimulated in DRGs derived from Tlr3–/– mice. Poly(I:C) stimulation showed no effect on neuronal sprouting in either WT or Tlr3–/– cells. ***P < 0.001. n = 26. One-way ANOVA with Tukey’s post hoc analysis (B, C, and E). CTR, control; SWT, shock wave therapy; XTT, (sodium 3′-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy6-nitro) benzene sulfonic acid hydrate).