MiR-615 Agomir Encapsulated in Pluronic F-127 Alleviates Neuron Damage and Facilitates Function Recovery After Brachial Plexus Avulsion

Abstract

AbstractBrachial plexus avulsion (BPA) is a devastating traumatic peripheral nerve injury complicated with paralysis of the upper extremity. We previously reported that leucine-rich repeat and immunoglobulin-like domain-containing NOGO receptor-interacting protein 1 (LINGO-1) has a potent role in inhibiting neuron survival and axonal regeneration after the central nervous system (CNS) damage and miR-615 is a potential microRNA (miRNA) negatively regulated LINGO-1. However, the effect of miR-615 in BPA remains to be elucidated. Accumulating evidence indicates that pluronic F-127 (PF-127) hydrogel could serve as a promising vehicle for miRNA encapsulation. Thus, to further explore the potential role of hydrogel-miR-615 in BPA-reimplantation, the present study established the BPA rat model and injected miR-615 agomir encapsulated by PF-127 hydrogel into the reimplantation site using a microsyringe. In this study, results indicated that hydrogel-miR-615 agomir effectively alleviated motoneuron loss by LINGO-1 inhibition, promoted musculocutaneous nerve regeneration and myelination, reduced astrocytes activation, promoted angiogenesis and attenuated peripheral amyotrophy, leading to improved motor functional rehabilitation of the upper extremity. In conclusion, our findings demonstrate that miR-615-loaded PF-127 hydrogel may represent a novel therapeutic strategy for BPA treatment.