Neurochemical Research

, Volume 40, Issue 5, pp 991–999 | Cite as

S100B and Glial Fibrillary Acidic Protein as Indexes to Monitor Damage Severity in an In Vitro Model of Traumatic Brain Injury

  • Valentina Di Pietro
  • Angela Maria Amorini
  • Giacomo Lazzarino
  • Kamal Makram Yakoub
  • Serafina D’Urso
  • Giuseppe Lazzarino
  • Antonio Belli
Original Article


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 (R2 = 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.


Biomarkers GFAP Hippocampal stretch injury S100B Traumatic brain injury 



We wish to thank the Wessex Medical Research Centre and Smile4rich for funding this study and for their support to our research.

Conflict of interest

The authors declare that they have no conflict of interest.

Animal Rights

All procedures used were in accordance with UK regulations under the Animals (Scientific Procedures) Act of 1986.


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Copyright information

© European Union 2015

Authors and Affiliations

  • Valentina Di Pietro
    • 1
  • Angela Maria Amorini
    • 2
  • Giacomo Lazzarino
    • 2
  • Kamal Makram Yakoub
    • 1
  • Serafina D’Urso
    • 3
  • Giuseppe Lazzarino
    • 3
  • Antonio Belli
    • 1
    • 4
  1. 1.Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental SciencesUniversity of BirminghamBirminghamUK
  2. 2.Institute of Biochemistry and Clinical BiochemistryCatholic University of RomeRomeItaly
  3. 3.Department of Biology, Geology and Environmental Sciences, Division of Biochemistry and Molecular BiologyUniversity of CataniaCataniaItaly
  4. 4.National Institute for Health Research Surgical Reconstruction and Microbiology Research CentreQueen Elizabeth HospitalBirminghamUK

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