Patterns of production of collagen-rich deposits in peripheral nerves in response to injury: A pilot study in a rabbit model.

Michael Rivlin,Jacob Tulipan,Andrzej Fertala,Pedro K Beredjiklian,Jolanta Fertala,James Kostas,Andrzej Steplewski,Andrew Miller,Mark L Wang

doi:10.1002/brb3.659

Michael Rivlin, Jacob Tulipan + Show 7 more

Open Access

https://doi.org/10.1002/brb3.659

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Abstract

IntroductionAlthough collagen‐rich deposits are the main component of neural scars, the patterns of their formation are ill defined. Essential to the biosynthesis of collagen fibrils are enzymes catalyzing posttranslational modifications and chaperones that control the formation of the collagen triple helix. Prolyl‐4‐hydroxylase (P4H) and heat shock protein‐47 (HSP47) play a key role, and their production is upregulated during scar formation in human tissues. Alpha smooth muscle actin (αSMA) is also produced during fibrotic processes in myofibroblasts that participate in fibrotic response. In injured peripheral nerves, however, the distribution of cells that produce these markers is poorly understood.MethodsThe goal of this study was to determine the distribution of the αSMA‐positive, HSP47‐positive, and the P4H‐positive cells to better understand the formation of collagen‐rich fibrotic tissue (FT) in response to peripheral nerve injury. To reach this goal, we employed a rabbit model of crush‐injury and partial‐transection injury of the sciatic nerves.ResultsOur study demonstrated that αSMA is expressed in a relatively small number of cells seen in neural FT. In contrast, cells producing P4H and HSP47 are ubiquitously present in sites of injury of the sciatic nerves.ConclusionWe contemplate that these proteins may serve as valuable markers that define fibrotic activities in the injured peripheral nerves.

Highlights

Collagen-rich deposits are the main component of neural scars, the patterns of their formation are ill defined
Many of the persistent functional deficits are attributed to neural fibrosis and scarring, which presents a mechanical barrier to peripheral nerve regeneration (Atkins et al, 2006)
The goal of this study was to determine the distributions of the αSMA-positive, heat shock protein-47 (HSP47)-positive, and the αβP4H-positive cells in response to Peripheral nerve injury (PNI), in order to better understand the formation of collagen-rich fibrotic tissue (FT) and to identify targets for potential therapeutic blockade of this process

Summary

| INTRODUCTION

Peripheral nerve injury (PNI) occurs in an estimated 2%–2.8% of patients with upper and lower extremity trauma, causing a significant burden of disease and disability (Noble, Munro, Prasad, & Midha, 1998). Many of the persistent functional deficits are attributed to neural fibrosis and scarring, which presents a mechanical barrier to peripheral nerve regeneration (Atkins et al, 2006). The goal of this study was to determine the distributions of the αSMA-positive, HSP47-positive, and the αβP4H-positive cells in response to PNI, in order to better understand the formation of collagen-rich fibrotic tissue (FT) and to identify targets for potential therapeutic blockade of this process. To achieve this goal, we employed rabbit models of crush-injury and partial- transection injury of the sciatic nerves

| MATERIALS AND METHODS

Findings

| DISCUSSION