Changes in spinal cord injury–induced gene expression in rat are strain-dependent

doi:10.1016/j.spinee.2005.05.379

The Spine Journal

Volume 6, Issue 2, March–April 2006, Pages 113-119

https://doi.org/10.1016/j.spinee.2005.05.379 Get rights and content

Abstract

Background and Context

The functional recovery of animals subject to experimental spinal cord injury (SCI) is dependent on the injury model as well as the species and strain of animal used. Previous studies have shown differences in rates and degree of recovery between rats of different strains.

Purpose

We sought to explore the hypothesis that differences in gene expression are associated with differences in functional recovery.

Study Design/Setting

Laboratory study involving cohorts of three different strains of rat.

Methods

We used the Impactor device to produce identical spinal cord contusion injuries in groups of Long Evans, Sprague-Dawley, and Lewis rats (10 each). The functional recovery of animals was assessed using the Basso, Beattie, and Bresnahan rating scale. Six weeks after injury, rats were killed and the spinal cords were harvested for deoxyribonucleic acid microarray analysis. Changes in gene expression compared with intraspecies controls (3 each) were assessed at the region of injury and at a rostral segment of the spinal cord. Selected genes were also studied with real-time polymerase chain reaction.

Results

We found that different strains tended to exhibit different patterns of functional recovery. There were differences between the strains in terms of gene expression.

Conclusions

These results emphasize the importance of testing novel therapies for SCI in a variety of animal species before introduction into human trials. Further research into the influence of several gene products on functional recovery is needed.

Introduction

Functional outcomes after spinal cord injury (SCI) have been shown to vary between animal species, injury type, injury severity, and animal age. In rat models of SCI, some measures of functional recovery, such as locomotor function and the development of allodynia, appear to be somewhat strain-dependent [1]. Some of these differences may be due to differences in animal size, regional anatomy, or local blood supply to the spinal cord. We hypothesized that some differences may be the result of differences in the molecular response to injury between strains.

Changes in the expression of genes and gene products have been studied immediately after SCI by a number of groups, including our own. Alteration in the expression of genes involved with inflammation, excitotoxicity, cell cycle functions, and nociception have been noted in the early stages after SCI in rats [2], [3], [4], [5], [6]. There is limited information available regarding changes in gene expression in chronically injured animals of any strain [7].

To explore our hypothesis that differences in functional outcome may be related to alterations in gene expression, we performed deoxyribonucleic acid microarray testing of cohorts of age-, weight-, and sex-matched Long Evans, Sprague-Dawley, and Lewis rats after a contusion SCI. Results were confirmed with real-time polymerase chain reaction (RTPCR) experiments using selected primers.

Section snippets

Experimental animals

Long Evans, Sprague-Dawley, and Lewis rats were housed and cared for in accordance with the Guide for the Care and Use of Laboratory Animals of the U.S. Department of Health and Human Services. All surgical procedures were performed in an aseptic manner and were approved by the Laboratory Animal Resources committee of the University of Wisconsin-Madison.

Spinal cord contusion injury

SCI was induced in adult male rats (272–320 g) with the MASCIS impactor (Impactor) as described previously [8], [9]. Under halothane anesthesia

Results

Of the 1,263 transcripts represented on the Affymetrix rat neurobiology GeneChip, only those genes that showed a present call in either the contused or sham groups (or both) were analyzed. Furthermore, only those transcripts that showed a fold-change of 2 or greater were included in the analysis. The data in the tables are presented as fold change versus sham controls. A value of 8.0 in the upregulated table, for example, means that the gene expression was eight times greater in the injured

Discussion

Differences in behavioral outcomes after SCI in rats of different strains have been documented by Mills et al. [1]. These authors assessed the development of mechanical and thermal allodynia at regular intervals through 5 weeks after either a contusion or hemisection injury in Long Evans, Wistar, and Sprague-Dawley rats. There were substantial differences noted in the percentage of animals of each strain that developed mechanical allodynia after a hemisection injury (40% of Long Evans vs. 75%

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Clinical StudiesChanges in spinal cord injury–induced gene expression in rat are strain-dependent

Abstract

Background and Context

Purpose

Study Design/Setting

Methods

Results

Conclusions

Introduction

Section snippets

Experimental animals

Spinal cord contusion injury

Results

Discussion

Neurosci Lett

Am J Hum Genet

Br J Anaesth

Strain and model differences in behavioral outcomes after spinal cord injury in rat

J Neurotrauma

Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss

Physiol Genomics

Gene profiling in spinal cord injury shows role of cell cycle neuronal death

Ann Neurol

Detection of gene expression pattern in the early stage after spinal cord injury by gene chip

Chinese J Traumatol

Genechip analysis after acute spinal cord injury in rat

J Neurochem

Clinical Studies
Changes in spinal cord injury–induced gene expression in rat are strain-dependent