LAUSR

BACKGROUND Cavernous nerve (CN) injury-induced erectile dysfunction (ED) caused by pelvic surgery or trauma is refractory to conventional medications and required an alternative treatment. Low-intensity pulsed ultrasound (LIPUS) is a noninvasive mechanical therapy that promotes nerve regeneration. OBJECTIVES To investigate the therapeutic effect and potential mechanism of LIPUS in the treatment of neurogenic erectile dysfunction. MATERIALS AND METHODS Thirty rats were randomly divided into the sham-operated group, bilateral CN injury (BCNI) group and BCNI + LIPUS group. The erectile function was assessed 3 weeks after daily LIPUS treatment. The penile tissues and CN tissues were harvested and subjected to histologic analysis. Primary Schwann cells (SCs) and explants were extracted from adult rats. The effects of LIPUS on proliferation, migration and NGF expression of SCs and axonal elongation was examined in vitro. RNA sequencing and western blot assay were applied to predict and verify the molecular mechanism of LIPUS-induced SCs activation. RESULTS Our study showed that LIPUS promoted SCs proliferation, migration and neurotrophic factor NGF expression. Meanwhile, LIPUS exhibits a stronger ability to enhance SCs-mediated neurite outgrowth of major pelvic ganglion (MPG) neurons and MPG/CN explants in vitro. In vivo experiments demonstrated that the erectile function of the rats in BCNI +LIPUS group were significantly higher than those in the BCNI groups. Moreover, the expression levels of smooth muscle and cavernous endothelium also increased significantly in the BCNI +LIPUS group. In addition, we observed the higher density and number of cavernous nerve regenerating axons in BCNI +LIPUS group, indicating that LIPUS promotes axonal regeneration following cavernous nerve injury in vivo. RNA sequencing analysis and bioinformatic analysis suggested that LIPUS might trigger the activation of the PI3K/Akt pathway. Western blot assay confirmed that LIPUS activated SCs through TrkB/Akt/CREB signaling. CONCLUSIONS LIPUS promoted nerve regeneration and ameliorated erectile function by enhancing SCs proliferation, migration and neurotrophic factor NGF expression. The TrkB/Akt/CREB axis is the possible mechanism of LIPUS-mediated SC activation. LIPUS-based therapy could be a novel potential treatment strategy for cavernous nerve injury-induced neurogenic ED. This article is protected by copyright. All rights reserved.