Deep Sequencing and Bioinformatic Analysis of Lesioned Sciatic Nerves after Crush Injury.

Abstract

The peripheral nerve system has an intrinsic regenerative capacity in response to traumatic injury. To better understand the molecular events occurring after peripheral nerve injury, in the current study, a rat model of sciatic nerve crush injury was used. Injured nerves harvested at 0, 1, 4, 7, and 14 days post injury were subjected to deep RNA sequencing for examining global gene expression changes. According to the temporally differential expression patterns of a huge number of genes, 3 distinct phases were defined within the post-injury period of 14 days: the acute, sub-acute, and post-acute stages. Each stage showed its own characteristics of gene expression, which were associated with different categories of diseases and biological functions and canonical pathways. Ingenuity pathway analysis revealed that genes involved in inflammation and immune response were significantly up-regulated in the acute phase, and genes involved in cellular movement, development, and morphology were up-regulated in the sub-acute stage, while the up-regulated genes in the post-acute phase were mainly involved in lipid metabolism, cytoskeleton reorganization, and nerve regeneration. All the data obtained in the current study may help to elucidate the molecular mechanisms underlying peripheral nerve regeneration from the perspective of gene regulation, and to identify potential therapeutic targets for the treatment of peripheral nerve injury.