Cerebral Injury Promotes Regeneration of The Brachial Plexus

Background: Our previous trial of contralateral seventh cervical nerve transfer (CC7) for spastic arm paralysis suggested that regeneration of the C7 nerve seems to be faster in patients undergoing nerve transfer due to cerebral injury compared to patients receiving surgery due to brachial plexus injury (BPI). This finding needs to be further verified, and the underlying mechanism remains largely unknown. The present study compared C7 regeneration between two groups of patients and animal models. Proteomics was utilized to reveal the mechanism mediating the promotion of C7 nerve regeneration. Methods: : We assessed Tinel’s sign in the arm after C7 transfer and compared the latency to the appearance of Tinel’s sign to evaluate regeneration. Traumatic brain injury (TBI) and BPI were induced in C57 mice to establish injury models. C7 regeneration was assessed by electrophysiology and histology. Enrichment analysis of the differentially expressed proteins identified by proteomics suggested altered inflammation related to TBI. qPCR and histology were performed to assess the inflammatory environment in the C7 nerve. We evaluated the influence of the contributing factor serum amyloid protein A1 (SAA1) on the regenerative ability and inflammatory response of the C7 nerve by electrophysiology, qPCR and histology. Results: : Faster C7 regeneration was identified in patients, which was further confirmed in mouse models by electrophysiological recordings and histology. Altered systemic inflammation, which led to increased M2 macrophage activation, may represent an underlying mechanism of increased regeneration. In mice, SAA1 facilitated C7 regeneration and interfered with macrophage polarization in vivo. Conclusions: : Altered inflammation promoted the regenerative capacity of the C7 nerve by altering macrophage behavior, and SAA1 may be a therapeutic target to improve the recovery of injured peripheral nerves.