Peripheral Blood Mononuclear Cells Regulate Differentially Expressed Proteins in the Proximal Sciatic Nerve of Rats after Transection Anastomosis

Pheripheral nerve injury (PNI) is a common disease that causes the partial loss of sensory, exercise, and autonomic nervous function. In clinical practice, accurate end-to-end neurorrhaphy of the epineurium without tension is the ideal treatment when there is no nerve defect. We have confirmed that peripheral blood mononuclear cells (PBMCs) can effectively improve nerve regeneration and motor function recovery after PNI. However, the global protein profile and signaling conduction pathways regulated by PBMCs remain unclear. This study employed the transection anastomosis model to detect the walking track analysis, gastrocnemius wet weight rate, and morphological examination in order to validate the effect of PBMCs on sciatic nerve injury in rats. Results showed that PBMCs improved nerve regeneration after sciatic nerve dissociation and anastomosis in rats, which reflected in the improvement of the sciatic nerve function index, wet weight rate of gastrocnemius muscles, muscle fiber structure, and the number of axons. We then used TMT labeling quantitative proteomics to explore the underlying mechanism by which PBMCs ameliorated sciatic nerve injury. Results showed that PBMCs regulated 40 differential proteins and the regulated proteins were primarily involved in the complement and coagulation cascade pathways, the notch signaling pathway, the renin angiotensin system, DNA replication, histidine metabolism, beta-alanine metabolism, and other types of O-glycan biosynthesis. Immunohistochemical results supported our findings on the changes in expression of Kininogen 1 and Psen1, the relationships between PNI and the notch pathway and the complement and coagulation level pathways. (C) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

The study demonstrates that peripheral blood mononuclear cells (PBMCs) can promote nerve regeneration and functional recovery in rats with sciatic nerve injury. Proteomics analysis reveals that PBMCs regulate pathways involved in complement and coagulation cascade, notch signaling, and other metabolic processes, contributing to the improvement of nerve injury treatment.