Open AccessShock 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
Author(s) -
Lobenwein Daniela,
Tepeköylü Can,
Kozaryn Radoslaw,
Pechriggl Elisabeth J.,
Bitsche Mario,
Graber Michael,
Fritsch Helga,
Semsroth Severin,
Stefanova Nadia,
Paulus Patrick,
Czerny Martin,
Grimm Michael,
Holfeld Johannes
Publication year - 2015
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.115.002440
Subject(s) - medicine , spinal cord , ischemia , neuroprotection , downregulation and upregulation , spinal cord injury , tlr4 , anesthesia , neuroscience , receptor , pharmacology , biology , biochemistry , psychiatry , gene
Background Paraplegia following spinal cord ischemia represents a devastating complication of both aortic surgery and endovascular aortic repair. Shock wave treatment was shown to induce angiogenesis and regeneration in ischemic tissue by modulation of early inflammatory response via Toll‐like receptor ( TLR) 3 signaling. In preclinical and clinical studies, shock wave treatment had a favorable effect on ischemic myocardium. We hypothesized that shock wave treatment also may have a beneficial effect on spinal cord ischemia. Methods and Results A spinal cord ischemia model in mice and spinal slice cultures ex vivo were performed. Treatment groups received immediate shock wave therapy, which resulted in decreased neuronal degeneration and improved motor function. In spinal slice cultures, the activation of TLR3 could be observed. Shock wave effects were abolished in spinal slice cultures from TLR 3 −/− mice, whereas the effect was still present in TLR 4 −/− mice. TLR 4 protein was found to be downregulated parallel to TLR 3 signaling. Shock wave–treated animals showed significantly better functional outcome and survival. The protective effect on neurons could be reproduced in human spinal slices. Conclusions Shock wave treatment protects from neuronal degeneration via TLR 3 signaling and subsequent TLR 4 downregulation. Consequently, it represents a promising treatment option for the devastating complication of spinal cord ischemia after aortic repair.