title: S100B and Glial Fibrillary Acidic Protein as Indexes to Monitor Damage Severity in an In Vitro Model of Traumatic Brain Injury.
abstract: Traumatic brain injury (TBI) is a leading and rising cause of death and disability worldwide. There is great interest in S100B and Glial Fibrillary Acid Protein (GFAP) as candidate biomarkers of TBI for diagnosis, triage, prognostication and drug development. However, conflicting results especially on S100B hamper their routine application in clinical practice. To try to address this question, we mimicked TBI damage utilizing a well-validated, simplified in vitro model of graded stretch injury induced in rat organotypic hippocampal slice cultures (OHSC). Different severities of trauma, from mild to severe, have been tested by using an equi-biaxial stretch of the OHSCs at a specified Lagrangian strain of 0 (controls), 5, 10, 20 and 50 %. OHSC were analysed at 3, 6, 18, 24, 48 and 96 h post-injury. Cell death, gene expressions and release into the culture medium of S100B and GFAP were determined at each time point. Gene expression and release of S100B slightly increased only in 20 and 50 % stretched OHSC. GFAP over-expression occurred in 10, 20 and 50 % and was inversely correlated with time post-injury. GFAP release significantly increased with time at any level of injury (p < 0.01 with respect to controls). Consequently, the total amount of GFAP released showed a strong linear relationship with the severity of injury (R(2) = 0.7662; p < 0.001). Under these experimental conditions, S100B seems to be useful in diagnosing only moderate to severe TBI-like injuries. Differently, GFAP demonstrates adequate biomarker requisites since its cellular release is affected by all grades of injury severity.
authors.affiliation: Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Pietro
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Amorini
authors.forename: Giacomo
authors.initials: G
authors.lastname: Lazzarino
authors.forename: Kamal Makram
authors.initials: KM
authors.lastname: Yakoub
authors.forename: Serafina
authors.initials: S
authors.lastname: D'Urso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lazzarino
authors.forename: Antonio
authors.initials: A
authors.lastname: Belli
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit / Q000096:biosynthesis*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat