Abstract

BackgroundCytokines are essential cellular modulators of various physiological and pathological activities, including peripheral nerve repair and regeneration. However, the molecular changes of these cellular mediators after peripheral nerve injury are still unclear. This study aimed to identify cytokines critical for the regenerative process of injured peripheral nerves.MethodsThe sequencing data of the injured nerve stumps and the dorsal root ganglia (DRGs) of Sprague-Dawley (SD) rats subjected to sciatic nerve (SN) crush injury were analyzed to determine the expression patterns of genes coding for cytokines. PCR was used to validate the accuracy of the sequencing data.ResultsA total of 46, 52, and 54 upstream cytokines were differentially expressed in the SNs at 1 day, 4 days, and 7 days after nerve injury. A total of 25, 28, and 34 upstream cytokines were differentially expressed in the DRGs at these time points. The expression patterns of some essential upstream cytokines are displayed in a heatmap and were validated by PCR. Bioinformatic analysis of these differentially expressed upstream cytokines after nerve injury demonstrated that inflammatory and immune responses were significantly involved.ConclusionsIn summary, these findings provide an overview of the dynamic changes in cytokines in the SNs and DRGs at different time points after nerve crush injury in rats, elucidate the biological processes of differentially expressed cytokines, especially the important roles in inflammatory and immune responses after peripheral nerve injury, and thus might contribute to the identification of potential treatments for peripheral nerve repair and regeneration.

Highlights

  • Cytokines are essential cellular modulators of various physiological and pathological activities, including peripheral nerve repair and regeneration

  • The expression levels of genes coding for these upstream cytokines were further examined, and differentially expressed upstream cytokines in the sciatic nerve (SN) and the Dorsal root ganglia (DRGs) at 1 day, 4 days, and 7 days after nerve injury were identified (Supplementary Table 1)

  • Detailed investigation of these differentially expressed upstream cytokines showed that the majority of cytokines were upregulated and only a few cytokines were downregulated in the SNs

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Summary

Introduction

Cytokines are essential cellular modulators of various physiological and pathological activities, including peripheral nerve repair and regeneration. The molecular changes of these cellular mediators after peripheral nerve injury are still unclear. This study aimed to identify cytokines critical for the regenerative process of injured peripheral nerves. Peripheral nerves are vulnerable tissues that are generally defenseless against traumatic injuries caused by bumping, stretching, crushing, and penetrating wounds as well as nontraumatic injuries caused by genetic, metabolic, infectious, and medically induced factors [1, 2]. Unlike central nerves, peripheral nerves can regenerate and achieve certain functional recovery after injury, full functional recovery is generally unexpected [3]. Axons of surviving neurons regrow toward target tissues for reinnervation [3, 4].

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