Time-Course Changes of Extracellular Matrix Encoding Genes Expression Level in the Spinal Cord Following Contusion Injury—A Data-Driven Approach

Abstract

The involvement of the extracellular matrix (ECM) in lesion evolution and functional outcome is well recognized in spinal cord injury. Most attention has been dedicated to the “core” area of the lesion and scar formation, while only scattered reports consider ECM modification based on the temporal evolution and the segments adjacent to the lesion. In this study, we investigated the expression profile of 100 genes encoding for ECM proteins at 1, 8 and 45 days post-injury, in the spinal cord segments rostral and caudal to the lesion and in the scar segment, in a rat model. During both the active lesion phases and the lesion stabilization, we observed an asymmetric gene expression induced by the injury, with a higher regulation in the rostral segment of genes involved in ECM remodeling, adhesion and cell migration. Using bioinformatic approaches, the metalloproteases inhibitor Timp1 and the hyaluronan receptor Cd44 emerged as the hub genes at all post-lesion times. Results from the bioinformatic gene expression analysis were then confirmed at protein level by tissue analysis and by cell culture using primary astrocytes. These results indicated that ECM regulation also takes place outside of the lesion area in spinal cord injury.

A Time-Course Study of the Expression Level of Synaptic Plasticity-Associated Genes in Un-Lesioned Spinal Cord and Brain Areas in a Rat Model of Spinal Cord Injury: A Bioinformatic Approach

“…At 45 DPL, same genes are differentially expressed rostrally and caudally to SCI site. In particular, only Timp1 remains up-regulated, as previously described [30], and Nr4a1 down-regulated in both segments; while Egr3 and Gnai1 are downregulated in the rostral and caudal segment, respectively. The different gene members of the EGR family of transcriptional regulators are involved in CNS function, and Egr3 is required specifically for short-term memory [34].…”

Spinal cord injury: molecular mechanisms and therapeutic interventions

“…62 The cell response is the basic unit in the pathophysiology of SCI and has temporal and spatial characteristics. 33,63 The elucidation of the cellular response, especially the response mechanisms of different cell subsets, is of great significance for finding effective intervention targets for SCI. The pathological mechanism of SCI discussed in this review mainly focuses on rodents.…”

Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation

“…To demonstrate the effect of SynCAM3 deletion, we evaluated the relationship between SynCAM3 and gene expression in the injured cord. The heat map visually showed dynamic changes in the expression of all genes at 2, 4, 7, and 14 DPI ( Figure 1 C) [ 34 , 35 ]. It was confirmed that the most genetic changes occurred at seven DPI, when the expression of SynCAM3 was the lowest after SCI.…”