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