Byline: Xiao-Qing. Cheng, Wen-Jing. Xu, Xiao. Ding, Gong-Hai. Han, Shuai. Wei, Ping. Liu, Hao-Ye. Meng, Ai-Jia. Shang, Yu. Wang, Ai-Yuan. Wang
In our previous study, we investigated the dynamic expression of cytokines in the distal nerve stumps after peripheral nerve injury using microarray analysis, which can characterize the dynamic expression of proteins. In the present study, we used a rat model of right sciatic nerve transection to examine changes in the expression of cytokines at 1, 7, 14 and 28 days after injury using protein microarray analysis. Interleukins were increased in the distal nerve stumps at 1-14 days post nerve transection. However, growth factors and growth factor-related proteins were mainly upregulated in the proximal nerve stumps. The P-values of the inflammatory response, apoptotic response and cell-cell adhesion in the distal stumps were higher than those in the proximal nerve stumps, but the opposite was observed for angiogenesis. The number of cytokines related to axons in the distal stumps was greater than that in the proximal stumps, while the percentage of cytokines related to axons in the distal stumps was lower than that in the proximal nerve stumps. Visualization of the results revealed the specific expression patterns and differences in cytokines in and between the proximal and distal nerve stumps. Our findings offer potential therapeutic targets and should help advance the development of clinical treatments for peripheral nerve injury. Approval for animal use in this study was obtained from the Animal Ethics Committee of the Chinese PLA General Hospital on September 7, 2016 (approval No. 2016-x9-07).
Peripheral nerve injury (PNI) is often caused by traffic accidents, trauma or surgery, resulting in pain and the loss of nerve function (Luo et al., 2020; Yuan et al., 2020). In contrast to the central nervous system (CNS), nerves in the peripheral nervous system have an inherent ability to regenerate. However, clinical therapy cannot completely restore the functional connections of nerves (Gruart et al., 2003). This is because the regeneration and functional connection of peripheral nerves involves a complex process that consists of macrophage invasion, axon degeneration and Schwann cell proliferation, as well as requiring a permissive microenvironment for axon growth (Zochodne, 2000; Parrinello et al., 2010; Rishal and Fainzilber, 2010).
Wallerian degeneration (WD) is common during peripheral nerve degeneration. As for spinal cord injury (Stoll et al., 2002), many studies have explored the cellular response and molecular mechanisms of WD after PNI (Rotshenker, 2011; Tricaud and Park, 2017; Wei et al., 2020). Soon after injury, a series of immune and inflammatory responses occur: the number of macrophages sharply increases, and they are recruited to the injury region; Schwann cells start to demyelinate and secrete numerous cytokines and growth factors; and these cells together digest myelin fragments shed by demyelinating Schwann cells (Yi et al., 2015). Many studies on nerve regeneration have focused on the microenvironment in the distal nerve stump (Wang et al., 2017; Xing et al., 2017). Yi et al. (2015) examined the differential expression of microRNAs at various time points after...