Abstract Details

Title A Comparison of Circulating microRNAs and Neurodegenerative Biomarkers in Traumatic Brain Injury

Topic Neuro Trauma, Critical Care, and Sports Neurology

Presentation(s) Neurocritical Care Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 021

Objective

To evaluate the utility of whole blood microRNAs (miRNAs) as biomarkers for diagnosis of traumatic brain injury (TBI).

Background

miRNAs are emerging diagnostic and prognostic biomarkers in a number of neurological disorders but have not been compared to protein biomarkers of TBI-related injury.

Design/Methods

Forty-nine participants admitted with an acute TBI (31[24-51]; 80% male) and 31 controls (27[24-36]; 81% male) were enrolled. The median GCS of TBI subjects was 15 (13-15) and 62% had TBI-related injury detected by head CT (CT+). Blood samples collected within 72 hours of injury were analyzed for miRNA (whole blood) and protein biomarkers (plasma). The Glasgow Outcome Scale-Extended (GOS-E) was completed ≥1 month after injury.

Results

A volcano plot was generated from differential expressions of normalized miRNA data to identify the highest performing miRNAs distinguishing TBI and control subjects (FDR≤0.01, log FC≥|1|). Based on data robustness and literature, 5 miRNAs (let-7a-5p, let-7b-5p, let-7i-5p, miR-126-3p, miR-23a-3p) were selected for which there were significant differences in the average count of all miRNAs (p<0.001) between TBI and control subjects but not CT-negative (CT-) and CT+ TBI subjects. Levels of GFAP, NfL, and UCHL1 were increased in TBI versus controls (p<0.001, effect size≥0.5) and in those with CT+ compared to CT- injuries (p=0.044, 0.044, 0.067, respectively). The miRNAs correlated weakly with the brain-derived protein biomarkers (miR-23a: p≤0.00029, τ_b≥0.275; let-7a: p≤0.017, τ_b≤-1.92; let-7b: p≤0.028, τ_b≤-0.178; let-7i: p≤0.01, τ_b≤-0.207; miR-126: p≤0.0025, τ_b≤-0.243). miRNA counts and protein levels did not differ between those with good recovery (GOS-E ≥7) versus moderate disability (GOS-E<7).

Conclusions

miRNAs from whole blood are promising biomarkers in TBI based on their ability to differentiate TBI from controls, even those without CT evidence of injury. Future work will focus on correlating miRNA and multiplexed biomarkers with MRI characteristics and patient outcomes to improve injury classification and prognostication.

Authors/Disclosures
Hannah H. Zamore (Case Western Reserve University MSTP) PRESENTER	Hannah Zamore has nothing to disclose.
Brigid A. Magdamo	Ms. Magdamo has nothing to disclose.
	No disclosure on file
	No disclosure on file
Erika Silverman (University of Pennsylvania)	Ms. Silverman has nothing to disclose.
Cian Dabrowski, MS	Cian Dabrowski has nothing to disclose.
	No disclosure on file
	No disclosure on file
Justin A. Morrison (Penn Presbyterian Medical Center)	Mr. Morrison has nothing to disclose.
Ramon R. Diaz-Arrastia, MD, PhD, FAAN (University of Pennsylvania)	Dr. Diaz-Arrastia has stock in BrainBox, LLC. Dr. Diaz-Arrastia has stock in Nia Therpeutics. The institution of Dr. Diaz-Arrastia has received research support from National Institutes of Health. The institution of Dr. Diaz-Arrastia has received research support from Department of Defense.
Danielle Sandsmark, MD	The institution of Dr. Sandsmark has received research support from NINDS. The institution of Dr. Sandsmark has received research support from BrainBox Solutions Inc. The institution of Dr. Sandsmark has received research support from Department of Defense.

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