title: Cell-free DNA as a marker for prediction of brain damage in traumatic brain injury in rats.
abstract: Traumatic brain injury (TBI) is a major cause of morbidity and mortality, and early predictors of neurological outcomes are of great clinical importance. Cell free DNA (CFD), a biomarker used for the diagnosis and monitoring of several diseases, has been implicated as a possible prognostic indicator after TBI. The purpose of this study was to determine the pattern and timing of CFD levels after TBI, and whether a relationship exists between the level of CFD and brain edema and neurological outcomes. Thirty-nine Sprague-Dawley rats were randomly assigned to two groups: rats in group 1 (sham group) were anesthetized and had a scalp incision without TBI, and rats in group 2 were anesthetized and had a scalp incision with TBI, which was induced by using a weight drop model that causes diffuse brain injury. A neurological severity score (NSS) was assessed at 1, 24, and 48 h after TBI. CFD was measured via blood samples drawn at t=0 (baseline), 12, 24, 48, 72, and 120 h after TBI. At 48 h after TBI, brain edema was determined in a subgroup of 11 rats by calculating the difference between rats' wet and dry brain weight. The significance of comparisons between and within groups (CFD levels, brain water content, and NSS) were determined using the Kruskal-Wallis, Mann-Whitney and Student t test. The correlation between CFD levels and the NSS, as well as between CFD levels and the extent of brain edema, was calculated using the Spearman and Pearson tests, respectively. Compared with baseline levels, the CFD levels in rats subjected to TBI were significantly increased at 24 and 48 h after TBI (p<0.01 and p<0.05, respectively). A positive correlation was demonstrated between CFD levels 24 h following TBI and the extent of brain edema (r=0.63, p<0.05), as well as between CFD levels and the NSS (r=0.79, p<0.005). In this study, we demonstrated an increase in CFD levels after TBI, as well as a correlation between CFD levels and brain edema and NSS. CFD levels may provide a quick, reliable, and simple prognostic indicator of neurological outcome in animals after TBI. Its role in humans has not been clearly elucidated, but has potentially significant clinical implications.
authors.affiliation: Division of Anesthesiology and Critical Care, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Ohayon
authors.forename: Matthew
authors.initials: M
authors.lastname: Boyko
authors.forename: Amit
authors.initials: A
authors.lastname: Saad
authors.forename: Amos
authors.initials: A
authors.lastname: Douvdevani
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Gruenbaum
authors.forename: Israel
authors.initials: I
authors.lastname: Melamed
authors.forename: Yoram
authors.initials: Y
authors.lastname: Shapira
authors.forename: Vivian I
authors.initials: VI
authors.lastname: Teichberg
authors.forename: Alexander
authors.initials: A
authors.lastname: Zlotnik
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001925:Brain Damage, Chronic / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D001929:Brain Edema / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D001930:Brain Injuries / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D002474:Cell-Free System / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000097:blood*; D004195:Disease Models, Animal; D008297:Male; D011237:Predictive Value of Tests; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D004247:DNA