Citation

Redell JB, Moore AN, Ward NH, Hergenroeder GW, Dash PK. J. Neurotrauma 2010; 27(12): 2147-2156.

Affiliation

University of Texas Health Science Center-Houston, Neurobiology and Anatomy, 6431 Fannin, Houston, Texas, United States, 77030; John.B.Redell@uth.tmc.edu.

Copyright

(Copyright © 2010, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2010.1481

PMID

20883153

Abstract

Circulating microRNAs (miRNAs) present in the serum/plasma are characteristically altered in many pathological conditions, and have been employed as diagnostic markers for specific diseases. We examined if relative plasma miRNA levels are altered in patients with traumatic brain injury (TBI) as compared to matched healthy volunteers, and their potential for use as diagnostic TBI biomarkers. The plasma miRNA profiles from severe TBI patients (GCS ≤ 8) and age-, gender-, and race-matched healthy volunteers were compared by microarray analysis. Of the 108 miRNAs identified in healthy volunteer plasma, 52 were altered after severe TBI, including 33 with decreased and 19 with increased relative abundance. An additional 8 miRNAs were detected only in the TBI plasma. We used quantitative RT-PCR to determine if circulating miRNAs could segregate TBI patients within the first 24 hr post-injury. Receiver Operating Characteristic analysis indicated that miR-16, miR-92a and miR-765 were good markers of severe TBI (0.89, 0.82, and 0.86 AUC values, respectively). Multiple logistic regression analysis revealed that combining these miRNAs markedly increased diagnostic accuracy (100% specificity and 100% sensitivity) compared to either healthy volunteers or orthopedic injury patients. In mild TBI patients (GCS>12), miR-765 levels were unchanged, while the levels of miR-92a and miR-16 were significantly increased within the first 24 hr of injury compared to healthy volunteers, and had AUC values of 0.78 and 0.82, respectively. Our results demonstrate that circulating miRNA levels are altered after TBI, providing a rich new source of potential molecular biomarkers. Plasma-derived miRNA biomarkers, used in combination with established clinical practices such as imaging, neurocognitive, and motor examinations, have the potential to improve TBI patient classification and possibly management.

Language: en