Authors :
Presenting Author: Anna-Maria Katsarou, MD – Albert Einstein College of Medicine
Mike Eklund, PhD – USUHS
Wenzhu Mowrey, PhD – Albert Einstein College of Medicine
Cesar Santana-Gómez, PhD – Department of Neurology, David Geffen School of Medicine, University of California
Idrish Ali, PhD – Monash University
Jesus-Servando Medel-Matus, PhD – UCLA
Cindy Santiago-Castaneda, MSc, PhD – Albert Einstein College of Medicine
Christopher Martinez-Aguirre, PhD – Albert Einstein College of Medicine
Wei Liu, BSc – Albert Einstein College of Medicine
I-Hsuan Lin, PhD – USUHS
Jesse McCullough, PhD – USUHS
Don Shin, BSc – UCLA
Peravina Thergarajan, PhD – Monash University
Emma Braine, PhD – Monash University
Xinyu Yu, PhD – Monash University
Nigel Jones, PhD – Monash University
Sandy Shultz, PhD – Monash University
David Wright, PhD – Monash University
Pablo Casillas-Espinosa, MD, PhD – Monash University
Terence O’Brien, MD – Monash University
Andrey Mazarati, PhD – UCLA
Solomon L. Moshé, MD – Albert Einstein College of Medicine
Denes Agoston, MD, PhD – USUHS
Aristea Galanopoulou, MD, PHD – Montefiore/ Albert Einstein College of Medicine
Rationale:
Moderate to severe traumatic brain injury (TBI) increases the risk for post-traumatic epilepsy (PTE). Elevated serum GFAP, UCHL1, and S100B levels within the first hours from TBI in humans indicate high risk for intracranial pathologies. The lateral fluid percussion injury (LFPI) model was optimized to reproduce intracranial hemorrhages that are epileptogenic. We investigated the temporal expression of candidate protein TBI biomarkers in the plasma of LFPI, SHAM or naïve CONTROL rats. LFPI rats also received treatments that are either used clinically in the acute post-TBI period, e.g. levetiracetam (LEV), or modify iron load from hemorrhages, i.e. the iron chelator deferiprone (DEF). Here, we explored the value of plasma GFAP, UCHL1, and S100B levels in differentiating TBI from SHAM or CONTROLs and the effects of LEV and DEF, using a multicenter, blinded study design.
Methods:
Sprague-Dawley male and female rats underwent left parietal 5mm craniotomy (SHAM, n=141), or LFPI (LFPI, n=540) or only blood collection (CONTROL, n=100) at 3 different sites (Einstein n=315, UCLA n=160, Monash n=336). LEV (200mg/kg/d), and/or DEF (7.6mg/kg/d) or vehicle (VEH) was administered with a bolus injection after the craniotomy/LFPI and SC minipump delivery for 7d (n=53-58 rats/group). Plasma was collected at baseline (BL) and at 2hr, 1d, 2d, 7d after craniotomy/LFPI. Protein biomarkers, including GFAP, S100B, and UCHL1, were analyzed with reverse-phase protein microarrays (RPPM, Agoston lab). The global model output method was adopted and further normalization was done across sites. Statistics included linear mixed model analyses. Statistical significance level was set at p< 0.05.