Shock waves promote spinal cord repair via TLR3
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
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
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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

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Figure 1

Improved locomotor function and decreased lesion size after treatment.

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Improved locomotor function and decreased lesion size after treatment. (...
(A) Mice were treated 2 weeks after spinal cord injury, and analyses were performed 10 weeks after treatment. (B) Gait analysis revealed improved motor scores in SWT-treated WT animals compared with controls, whereas SWT had no effect in Tlr3-deficient mice. *P < 0.05. n = 4 (WT CTR), n = 6 (WT SWT), n = 7 (Tlr3–/– CTR), n = 5 (Tlr3–/– SWT). (C) Covered distance in automated open-field analysis was significantly increased by SWT of WT animals. SWT had no beneficial effect in Tlr3–/– mice. *P < 0.05, *** P < 0.001. n = 4 (WT CTR), n = 7 (WT SWT), n = 7 (Tlr3–/– CTR), n = 5 (Tlr3–/– SWT). (D) For quantification of lesion size, we performed MRI analysis of the spinal cord (original magnification, ×3.5, insets). (E) SWT resulted in a significant reduction of spinal cord lesion size 10 weeks after injury. There was no effect of SWT on lesion size in Tlr3–/– mice. **P < 0.01. n = 7 (WT CTR), n = 11 (WT SWT), n = 5 (Tlr3–/– CTR), n = 6 (Tlr3–/– SWT). (F) SWT resulted in decreased bladder volumes in WT but not Tlr3–/– mice. ***P < 0.001. n = 7 (WT CTR), n = 11 (WT SWT), n = 5 (Tlr3–/– CTR), n = 6 (Tlr3–/– SWT). One-way ANOVA with Tukey’s post hoc analysis (B, C, E, and F). CTR, control; SWT, shock wave therapy.