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Valproic Acid Treatment Decreases Serum GFAP And UCH‐L1 Levels In Swine Subjected To Traumatic Brain Injury

Journal Of Neurotrauma | February 07, 2018

Dr. Frederick Kofi Korley, Dr. Vahagn C. Nikolian, Dr. Aaron M. Williams, Dr. Isabel S. Dennahy, Mr. Michael Weykamp, and Dr. Hasan B Alam
Journal of Neurotrauma
DOI: 10.1089/neu.2017.5581


The primary aim of this study was to examine the effects of valproic acid (VPA) treatment on serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NF-L) levels. To achieve this aim, we obtained serum samples from: (1) ten Yorkshire swine subjected to controlled cortical impact (CCI) TBI + polytrauma and randomized to receive either normal saline (NS) + VPA (n=5) or NS alone (n=5) and (2) five additional swine subjected to CCI TBI without polytrauma and treated with VPA. GFAP and NF-L levels were measured in samples obtained from baseline until 10 days post-injury using a digital immunoassay from Quanterix Corporation. We found that elevated GFAP and NF-L levels were first detected at 2 hours post-injury; and peaked at 24 hours and 72 hours respectively. GFAP levels returned to baseline levels by day-10, while NF-L remained elevated at day-10. In TBI + polytrauma swine, the magnitude and duration of biomarker elevation, quantified by the area under the biomarker concentration versus time curve during the first 10-days (AUC0-10days), was higher in the NS group compared to the VPA group. For GFAP, the AUC0-10days was 45,535 (IQR: 35,741–105,711) and 22,837 [IQR: 8,082–46,627] for the NS and NS+VPA groups respectively. For NF-L, the AUC0-10days was 43,073 [IQR: 18,739–120,794] and 4,475 [2,868–11,157] for the NS and NS+VPA groups respectively. Twenty-four hour GFAP and NFL levels had the strongest correlation with lesion size and time to normalization of behavior. Accordingly, we conclude that treatment with VPA results in significantly lower serum GFAP and NF-L levels. The time-point at which GFAP and NF-L levels have the strongest correlation with outcome is 24 hours post-injury.