title: Correlation of mechanical impact responses and biomarker levels: A new model for biomarker evaluation in TBI.
abstract: A modified Marmarou impact acceleration model was used to help screen biomarkers to assess brain injury severity. Anesthetized male Sprague-Dawley rats were subjected to a closed head injury from 1.25, 1.75 and 2.25 m drop heights. Linear and angular responses of the head were measured in vivo. 24h after impact, cerebrospinal fluid (CSF) and serum were collected. CSF and serum levels of phosphorylated neurofilament heavy (pNF-H), glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), and amyloid beta (Aβ) 1-42 were assessed by enzyme-linked immunosorbent assay (ELISA). Compared to controls, significantly higher CSF and serum pNF-H levels were observed in all impact groups, except between 1.25 m and control in serum. Furthermore, CSF and serum pNF-H levels were significantly different between the impact groups. For GFAP, both CSF and serum levels were significantly higher at 2.25 m compared to 1.75 m, 1.25 m and controls. There was no significant difference in CSF and serum GFAP levels between 1.75 m and 1.25 m, although both groups were significantly higher than control. TBI rats also showed significantly higher levels of IL-6 versus control in both CSF and serum, but no significant difference was observed between each impact group. Levels of Aβ were not significantly different between groups. Pearson's correlation analysis showed pNF-H and GFAP levels in CSF and serum had positive correlation with power (rate of impact energy), followed by average linear acceleration and surface righting (p<0.01), which were good predictors for traumatic axonal injury according to histologic assessment in our previous study, suggesting that they are directly related to the injury mechanism. The model used in this study showed a unique ability in elucidating the relationship between biomarker levels and severity of the mechanical trauma to the brain.
authors.affiliation: Department of Biomedical Engineering, Wayne State University, 818 W. Hancock Street, Detroit, MI 48201, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, Wayne State University, 818 W. Hancock Street, Detroit, MI 48201, United States. Electronic address: lzhang@wayne.edu.
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Wayne State University, 818 W. Hancock Street, Detroit, MI 48201, United States.
authors.forename: Srinivasu
authors.initials: S
authors.lastname: Kallakuri
authors.affiliation: Department of Biomedical Engineering, Wayne State University, 818 W. Hancock Street, Detroit, MI 48201, United States.
authors.forename: Abigail
authors.initials: A
authors.lastname: Cohen
authors.affiliation: Department of Biomedical Engineering, Wayne State University, 818 W. Hancock Street, Detroit, MI 48201, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Cavanaugh
mesh_terms: D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001696:Biomechanical Phenomena / Q000502:physiology*; D001930:Brain Injuries / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000097:blood / Q000134:cerebrospinal fluid; D006358:Hot Temperature / Q000009:adverse effects; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D016900:Neurofilament Proteins / Q000097:blood / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid; D051381:Rats; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C051774:neurofilament protein H
keywords: Cerebrospinal fluid biomarker; Head impact kinematics; Rodent; Serum biomarker, head impact acceleration model; Traumatic brain injury