title: Biomarkers track damage after graded injury severity in a rat model of penetrating brain injury.
abstract: The goal of this project was to determine whether biochemical markers of brain damage can be used to diagnose and assess the severity of injury in a rat model of penetrating ballistic-like brain injury (PBBI). To determine the relationship between injury magnitude and biomarker levels, rats underwent three discrete PBBI severity levels defined by the magnitude of the ballistic component of the injury, calibrated to equal 5%, 10%, or 12.5% of total rat brain volume. Cortex, cerebrospinal fluid (CSF), and blood were collected at multiple time points. Levels of three biomarkers (αII-spectrin breakdown product [SBDP150], glial fibrillary acidic protein [GFAP], and ubiquitin C-terminal hydrolase-L1 [UCH-L1]), were measured using quantitative immunoblotting and/or enzyme-linked immunosorbent assays. In injured cortex, SBDP150 and GFAP levels were increased significantly over controls. Cortical SBDP150 was elevated at 1 day but not 7 days, and GFAP at 7 days but not 1 day. At their respective time points, mean levels of SBDP150 and GFAP biomarkers in the cortex rose stepwise as injury magnitude increased. In the CSF, increasing severity of PBBI was associated with increasing concentrations of both neuronal and glial biomarkers acutely at 1 day after injury, but no trends were observed at 7 days. In plasma, SBDP150 was elevated at 5 min after 10% PBBI and at 6 h after 12.5% PBBI. UCH-L1 levels in plasma were elevated acutely at 5 min post-injury reflecting injury severity and rapidly decreased within 2 h. Overall, our results support the conclusion that biomarkers are effective indicators of brain damage after PBBI and may also aid in the assessment of injury magnitude.
authors: Banyan Biomarkers, Inc., Alachua, Florida, USA. szoltewicz@banyanbio.com
authors: J Susie
authors: JS
authors: Zoltewicz
authors: Stefania
authors: S
authors: Mondello
authors: Boxuan
authors: B
authors: Yang
authors: Kimberly J
authors: KJ
authors: Newsom
authors: Firas
authors: F
authors: Kobeissy
authors: Changping
authors: C
authors: Yao
authors: Xi-Chun May
authors: XC
authors: Lu
authors: Jitendra R
authors: JR
authors: Dave
authors: Deborah A
authors: DA
authors: Shear
authors: Kara
authors: K
authors: Schmid
authors: Virginia
authors: V
authors: Rivera
authors: Terri
authors: T
authors: Cram
authors: Jixiang
authors: J
authors: Seaney
authors: Zhiqun
authors: Z
authors: Zhang
authors: Kevin K W
authors: KK
authors: Wang
authors: Ronald L
authors: RL
authors: Hayes
authors: Frank C
authors: FC
authors: Tortella
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis*; D020197:Head Injuries, Penetrating / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013049:Spectrin / Q000032:analysis*; D043222:Ubiquitin Thiolesterase / Q000032:analysis*
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; C482860:UCHL1 protein, human; D013049:Spectrin; D043222:Ubiquitin Thiolesterase