RESUMO
Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.
RESUMO
OBJECTIVES: The primary objective of this study was to define the anatomy of the musculocutaneous nerve as it innervates the biceps and brachialis muscles in relation to nerve transfer surgery in brachial plexus injury.METHODS: Surgical dissection of the musculocutaneous nerve of both upper extremities of 34 embalmed cadavers was performed to define the anatomy of the musculocutaneous nerve as it supplies the biceps and the brachial muscles. Among the data that we noted were the distance where the branch of the biceps and branchialis took off from the musculocutaneous nerve from the coracoids, which was the bony landmark.RESULTS: There were 17 males and 17 females with a total of 65 musculocutaneous nerve to biceps muscle had an average distance of 10.9cm and a median of 11.0cm±1.83cm (range, 6.5-14.2 cm) from the coracoid. The branching of musculocutaneous nerve to the brachialis had an average distance of 15.1 cm and a median 15.5cm±1.72cm (range, 12.7-21.0cm) from the coracoid. Transferring the fascicles of the ulnar nerve to the biceps branch and a fascicle of the median nerve to the brachialis branch is fairly easy since both nerves are within the vicinity of respective recipient site.CONCLUSION: The anatomy of the musculocutaneous nerve as it supplies the elbow flexors is fairly consistent and there is little discrepancy between cadaveric specimens.
