We have taken shock waves for tissue regeneration one step further and have adapted them for the regeneration of spinal cord ischemia after aortic dissection or aortic surgery. We could show enhanced neuronal sprouting, limitation of neuronal degeneration and improvement of motor function in an ischemic and traumatic model of murine spinal cord injury7. We could identify an innate mechanism of regeneration, conserved in zebrafish, mice and humans. Expression of inflammatory cytokines including IL-6 lead to angiogenesis, recruitment of progenitor cells and limitation of secondary injury to the spinal cord. SWT reduced the number of reactive oxygen species positive cells and apoptosis upon ischemia via induction of the antioxidative factor nuclear factor erythroid 2-related factor 2. Inhibition or deletion of tlr3 impaired axonal growth after spinal cord lesion in zebrafish, whereas tlr3 stimulation enhanced spinal regeneration8.
Out of a clinical need we translated our preclinical results into the clinical setting and treated in a first-in-human experience five patients with spinal cord ischemia after aortic dissection with shock wave therapy with promising results for safety and feasibility9. This new treatment option might constitute a potent novel therapeutic approach to alleviate oxidative damage, reduce secondary neuronal damage and thus, preserve spinal cord tissue and function. In a next step, we aim to prove its efficacy in a prospective, randomized setting.
Key papers:
Gollmann-Tepekoylu C, Nagele F, Graber M, et al. Shock waves promote spinal cord repair via TLR3. JCI Insight 2020;5(15). DOI: 10.1172/jci.insight.134552.
Lobenwein D, Tepekoylu C, Kozaryn R, et al. Shock Wave Treatment Protects From Neuronal Degeneration via a Toll-Like Receptor 3 Dependent Mechanism: Implications of a First-Ever Causal Treatment for Ischemic Spinal Cord Injury. Journal of the American Heart Association2015;4(10):e002440. DOI: 10.1161/JAHA.115.002440.
Graber M, Nagele F, Rohrs BT, et al. Prevention of Oxidative Damage in Spinal Cord Ischemia Upon Aortic Surgery: First-In-Human Results of Shock Wave Therapy Prove Safety and Feasibility. Journal of the American Heart Association 2022;11(20):e026076. DOI: 10.1161/JAHA.122.026076.