Complement cascade on severe traumatic brain injury patients at the chronic unconscious stage: implication for pathogenesis

ABSTRACT

Background: Patients who awake from severely traumatic brain injury (TBI) may remain unconscious for many years. Although behavioral assessment and functional imaging are currently used as diagnostic tools, the molecular basis underlying chronic condition has yet to be explored.

Method: Plasma samples were obtained at 3 time points (1, 3 and 6 months) from 18 patients with chronic disorders of consciousness who survived severe TBI, and 6 healthy volunteers. A coupled isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics approach was used to screen differentially expressed proteins (DEPs) between patients and controls. Potential molecular mechanisms were further discussed through bioinformatics analyses.

Result: In total, 300 plasma proteins <1% false discovery rates were identified and 32 proteins were consistently altered between patients and controls. Biological pathway analysis revealed that the DEPs were predominantly involved in complement cascade.

Conclusions: This study discussed potential mechanisms of complement cascade underlying chronic stage in severe TBI.

KEYWORDS:

• Complement cascade
• chronic disorders of consciousness
• severe traumatic brain injury
• iTRAQ
• proteomics
• plasma

Acknowledgments

The authors wish to thank the patients and volunteers for participating in this study.

Declaration of Interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Author contributions

BWX and HFP were responsible for study design. HFP, GJ and MFX were responsible for data acquisition, analysis, and interpretation. BWX and ZH drafted the manuscript. ZH and LBY were responsible for critical revision of the manuscript. All authors read and approved the manuscript for publication.

Ethical approval and consent to participate

Written informed consent was obtained from the patients’ legal guardians and healthy volunteers. This study was approved by the Ethical Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University and Hangzhou Hospital of Zhejiang CAPR (Reference Number: 2,015,310).

Additional information

Funding

This work was supported by grants from the Science and Technology Plan of Zhejiang Province (2017C03011).