Spatial and temporal expression levels of specific microRNAs in a spinal cord injury mouse model and their relationship to the duration of compression.

BACKGROUND CONTEXT

MicroRNAs, a class of small nonprotein-coding RNAs, are thought to control gene translation into proteins. The latter are the ultimate effectors of the biochemical cascade occurring in any physiological and pathological process. MicroRNAs have been shown to change their expression levels during injury of spinal cord in contusion rodent models. Compression is the most frequent mode of damage of neural elements in spinal cord injury. The cellular and molecular changes occurring in the spinal cord during prolonged compression are not very well elucidated. Understanding the underlying molecular events that occur during sustained compression is paramount in building new therapeutic strategies.

PURPOSE

The purpose of our study was to probe the relationship between the expression level changes of different miRNAs and the timing of spinal cord decompression in a mouse model.

STUDY DESIGN

A compression spinal cord injury mouse model was used for the study.

METHODS

A laminectomy was performed in the thoracic spine of C57BL/6 mice. Then, the thecal sac was compressed to create the injury. Decompression was performed early for one group and it was delayed in the second group. The spinal cord at the epicenter of the injury and one level rostral to it were removed at 3, 6, and 24 hours after trauma, and RNA was extracted. Expression levels of six different microRNAs and the relationship to the duration of compression were analyzed. This work was supported in part by the University Research Council Grants Program at the University of Texas Health Science Center San Antonio (Grant 130267). There are no specific conflicts of interest to be disclosed for this work.

RESULTS

Expression levels of microRNAs in the prolonged compression of spinal cord model were significantly different compared with the expression levels in the short duration of compression spinal cord injury model. Furthermore, microRNAs show a different expression pattern in different regions of the injured spinal cord.

CONCLUSIONS

Our findings demonstrate that spinal cord compression causes alterations in the expression of different miRNAs in the acute phase of injury. Their expression is related to the duration of the compression of the spinal cord. These findings suggest that early decompression of the spinal cord may have an important modulating effect on the molecular cascade triggered during secondary injury through the changes in expression levels of specific microRNAs.