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

International Journal of Molecular Sciences, 2021 · DOI: https://doi.org/10.3390/ijms22041744 · Published: February 9, 2021

Spinal Cord Injury Genetics

Simple Explanation

This study investigates how the extracellular matrix (ECM), which is the material surrounding cells in the spinal cord, changes after a spinal cord injury (SCI). The researchers looked at the activity of genes that control ECM proteins at different times after injury. They found that the injury causes changes in gene activity related to ECM remodeling, cell adhesion, and migration, particularly in the area of the spinal cord closer to the head (rostral) compared to the tail (caudal). Two molecules, Timp1 and Cd44, appear to be central in these ECM changes, suggesting they play a key role in how the spinal cord responds to injury. The researchers confirmed these findings by looking at protein levels in the spinal cord tissue and in astrocyte cells grown in the lab.

Study Duration

45 days

Participants

Female CD-Sprague Dawley rats (200–250 g)

Evidence Level

Not specified

Key Findings

1
There is 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.
2
The metalloproteases inhibitor Timp1 and the hyaluronan receptor Cd44 emerged as the hub genes at all post-lesion times.
3
ECM regulation also takes place outside of the lesion area in spinal cord injury.

Research Summary

The study investigates 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. These results indicated that ECM regulation also takes place outside of the lesion area in spinal cord injury.

Practical Implications

Understanding SCI Evolution

Provides insights into the complex molecular events following SCI, particularly the role of ECM components.

Therapeutic Targets

Identifies Timp1 and Cd44 as potential therapeutic targets for SCI, focusing on ECM remodeling.

Regenerative Medicine

Highlights the importance of considering temporal and anatomical specificity in regenerative medicine approaches for SCI, including biomaterial design.

Study Limitations

1
Focus on protein component of the ECM through gene expression modulation and does not consider the hyaluronan component.
2
Lack of correlation between the single gene expression analysis and the motor-functional BBB score.
3
The study was conducted on a rat model, and findings may not directly translate to human SCI due to differences in pathophysiology and recovery mechanisms.

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