Roles of Macrophages and Their Interactions with Schwann Cells After Peripheral Nerve Injury.

The adult peripheral nervous system has a significant ability for regeneration compared to the central nervous system. This is related to the unique neuroimmunomodulation after peripheral nerve injury (PNI). Unlike the repair of other tissues after injury, Schwann cells (SCs) respond immediately to the trauma and send out signals to precisely recruit macrophages to the injured site. Then, macrophages promote the degradation of the damaged myelin sheath by phagocytosis of local debris. At the same time, macrophages and SCs jointly secrete various cytokines to reconstruct a microenvironment suitable for nerve regeneration. This unique pathophysiological process associated with macrophages provides important targets for the repair and treatment of PNI, as well as an important reference for guiding the repair of other nerve injuries. To understand these processes more systematically, this paper describes the characteristics of macrophage activation and metabolism in PNI, discusses the underlying molecular mechanism of interaction between macrophages and SCs, and reviews the latest research progress of crosstalk regulation between macrophages and SCs. These concepts and therapeutic strategies are summarized to provide a reference for the more effective use of macrophages in the repair of PNI.

Long non-coding RNAs influence aging process of sciatic nerves in SD rats.

OBJECTIVES: To investigate the long non-coding RNAs (lncRNAs) changes in the sciatic nerve (SN) in Sprague Dawley (SD) rats during aging. METHODS: Eighteen healthy SD rats were selected at the age of 1 month (1M) and 24 months (24M) and SNs were collected. High-throughput transcriptome sequencing and bioinformatics analysis were performed. Protein-protein interaction (PPI) networks and competing endogenous RNA (ceRNA) networks were established according to differentially expressed genes (DEGs). RESULT: As the length of lncRNAs increased, its proportion to the total number of lncRNAs decreased. A total of 4079 DElncRNAs were identified in Con vs. 24M. GO analysis was primarily clustered in nerve and lipid metabolism, extracellular matrix, and vascularization-related fields. There were 17 nodes in the PPI network of the target genes of up-regulating genes including Itgb2, Lox, Col11a1, Wnt5a, Kras, etc. Using quantitative RT-PCR, microarray sequencing accuracy was validated. There were 169 nodes constructing the PPI network of down-regulated target genes, mainly including Col1a1, Hmgcs1, Hmgcr. CeRNA interaction networks were constructed CONCLUSION: Lipid metabolism, angiogenesis, and ECM fields might play an important role in the senescence process in SNs. Col3a1, Serpinh1, Hmgcr, and Fdps could be candidates for nerve aging research.

Interactions Among Nerve Regeneration, Angiogenesis, and the Immune Response Immediately After Sciatic Nerve Crush Injury in Sprague-Dawley Rats.

To preliminarily explore the primary changes in the expression of genes involved in peripheral nerve processes, namely, regeneration, angiogenesis, and the immune response, and to identify important molecular therapeutic targets, 45 Sprague-Dawley (SD) rats were randomly divided into a control group and an injury group. In the injury group, tissue samples were collected at 4 and 7 days after the injury for next-generation sequencing (NGS) analysis combined with gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Venn diagram construction to identify the differentially expressed mRNAs (DEmRNAs) associated with regeneration, angiogenesis, and the immune response of the nerve. The expression of genes in the distal and proximal ends of the injured nerve after injury was analyzed by qRT-PCR. NGS revealed that compared with the control group, the injury group had 4020 DEmRNAs 4 days after injury and 3278 DEmRNAs 7 days after injury. A bioinformatics analysis showed that C-C chemokine receptor type 5 (CCR5), Thy1 cell surface antigen (Thy1), Notch homolog 1 (Notch1), and semaphorin 4A (Sema4A) were all associated with regeneration, angiogenesis, and the immune response of the nerve at both 4 and 7 days after injury, but qPCR revealed no significant difference in the expression of Thy1 (P = 0.29) or Sema4A (P = 0.82) in the proximal end, whereas a significant difference was observed in CCR5 and Notch1 (P < 0.05). The trend in the Notch1 change was basically consistent with the RNA-seq result after injury, which implied its indispensable role during endothelial cell proliferation and migration, macrophage recruitment, and neurotrophic factor secretion.