Low-intensity extracorporeal shock wave therapy promotes recovery of sciatic nerve injury and the role of mechanical sensitive YAP/TAZ signaling pathway for nerve regeneration

Background:Histological and functional recovery after peripheral nerve injury(PNI)is of significant clinical value as delayed surgical repair and longer distances to innervate terminal organs may account for poor outcomes.Low-intensity extracorporeal shock wave therapy(LiESWT)has already been proven to be beneficial for injured tissue recovery on various pathological conditions.The objective of this study was to explore the potential effect and mechanism of LiESWT on PNI recovery.Methods:In this project,we explored LiESWT’s role using an animal model of sciatic nerve injury(SNI).Shockwave was delivered to the region of the SNI site with a special probe at 3 Hz,500 shocks each time,and 3 times a week for 3 weeks.Rat Schwann cells(SCs)and rat perineurial fibroblasts(PNFs)cells,the two main compositional cell types in peripheral nerve tissue,were cultured in vitro,and LiESWT was applied through the cultured dish to the adherent cells.Tissues and cell cultures were harvested at corresponding time points for a reverse transcription-polymerase chain reaction,Western blotting,and immunofluorescence staining.Multiple groups were compared by using one-way analysis of variance followed by the Tukey-Kramer test for post hoc comparisons.Results:LiESWT treatment promoted the functional recovery of lower extremities with SNI.More nerve fibers and myelin sheath were found after LiESWT treatment associated with local upregulation of mechanical sensitive yes-associated protein(YAP)/transcriptional co-activator with a PDZ-binding domain(TAZ)signaling pathway.In vitro results showed that SCs were more sensitive to LiESWT than PNFs.LiESWT promoted SCs activation with more expression of p75(a SCs dedifferentiation marker)and Ki67(a SCs proliferation marker).The SCs activation process was dependent on the intact YAP/TAZ signaling pathway as knockdown of TAZ by TAZ small interfering RNA significantly attenuated this process.Conclusion:The LiESWT mechanical signal perception and YAP/TAZ upregulation in SCs might be one of the underlying mechanisms for SCs activation and injured nerve axon regeneration.

Comparative study of intracavernous pressure and cavernous pathology after bilateral caver nous n erve crushing and resection in rats

This study aimed to compare the effects of bilateral cavernous nerve crushing(BCNC)and bilateral cavernous nerve resection(BCNR)on intracavernous pressure(ICP)and cavernous pathology in rats and to explore the optimal treatment time for the BCNC and BCNR models.Seventy-two male rats aged 12 weeks were randomly divided into three equal groups:Sham(both cavernous nerves exposed only),BCNC(BCN crushed for 2 min),and BCNR(5 mm of BCN resected).Erectile function was then measured at 1 week,3 weeks,and 5 weeks after nerve injury,and penile tissues were harvested for histological and molecular analyses by immunohistochemistry,immuno fluoresce nee,Western blot,and cytokine array.We found that erectile function parameters including the maximum,area,and slope of ICP/mean arterial pressure(MAP)significantly decreased after BCNR and BCNC at 1 week and 3 weeks.At 5 weeks,no significant differences were observed in ICP/MAP between the BCNC and Sham groups,whereas the ICP/MAP of the BCNR group remained significantly lower than that of the Sham group.After BCNC and BCNR,the amount of neuronal-nitric oxide synthase-positive fibers,smooth muscle cells,and endothelial cells decreased,whereas the amount of collage n III con tent increased.These pathological cha nges recovered over time,especially in the BCNC group.Our fin dings demonstrate that BCNC leads to acute and reversible erectile dysfunction,thus treatme nt time should be restricted to the first 3 weeks post-BCNC.In contrast,the self-healing ability of the BCNR model is poor,making it more suitable for long-term treatment research.