Thymosin beta 4 induces significant changes in the plasma miRNA profile following severe traumatic brain injury in the rat lateral fluid percussion injury model

ABSTRACT

Objectives: Thymosin beta 4 (Tβ4) has demonstrated neuroprotective potential in models of neurlogical injury. The neuroprotective potential of Tβ4 has been associated with increased miR-200a and miR-200b within the brain following stroke. Here we tested the hypothesis that Tβ4 treatment could also alter miRNA profiles within the plasma following severe traumatic brain injury (TBI).

Methods: We used the rat lateral fluid percusion injury model of severe TBI to test this hypothesis. Highly sensitive and quantitative droplet digital polymerase chain reaction (ddPCR) was used to measure the plasma concentrations of miR-200 family members. In addition, we conducted RNAseq analysis of plasma miRNA to further identify changes associated with TBI and treatment with Tβ4.

Results: ddPCR demonstrated that miR-200a-3p andmiR-200b-3p were both significantly increased in plasma following treatment with Tβ4 after severe TBI. RNAseq analysis suggested that miR-300-3p and miR-598-3p increased while miR-450-3p and miR-194-5p significantly decreased following TBI. In contrast, miR-194-5p significantly increased in Tβ4 treated rats following TBI. In addition, we identified nine plasma miRNAs whose expression significantly changed following treatment with Tβ4.

Conclusions: Tβ4 treatment significantly increased plasma levels of miR-200a-3p and miR-200b-3p, while RNAseq analysis identified miR-194-5p as a candidate miRNA that may be critical for neuroprotection.

KEYWORDS:

• Microrna
• plasma
• thymosin beta 4
• traumatic brain injury

Author contributions

All authors contributed either intellectually or technically to this work.

Declaration of Interest

D. Poulsen serves part time as Chief Science Officer for NeuroTrauma Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Referee disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported in part by the New York State Center of Excellence in Bioinformatics and Life Sciences at the University of Buffalo and by the Department of Neurosurgery, State University of New York at Buffalo. This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease and is funded by SciClone Pharmaceuticals.