Valproic Acid Treatment Decreases Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels in Swine Subjected to Traumatic Brain Injury.

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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) 10 Yorkshire swine subjected to controlled cortical impact traumatic brain injury (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 h post-injury; and peaked at 24 h and 72 h 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 with 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 NF-L 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 h post-injury.