Operation Brain Trauma Therapy: An Exploratory Study of Levetiracetam Treatment Following Mild Traumatic Brain Injury in the Micro Pig.

作者: Patrick M. Kochanek , Karen Gorse , Stefania Mondello , Ronald Hayes , John Povlishock

DOI: 10.3389/FNEUR.2020.586958

关键词:

摘要: Operation Brain Trauma Therapy (OBTT) is a drug- and biomarker-screening consortium intended to improve the quality of preclinical studies provide rigorous framework increase translational potential experimental traumatic brain injury (TBI) treatments. Levetiracetam (LEV) an antiepileptic agent that was fifth drug tested by OBTT in three independent rodent models moderate severe TBI. To date, LEV has been most promising therefore advanced testing pig. Adult male micro pigs were subjected mild central fluid percussion followed post-injury intravenous infusion either 170 mg/kg or vehicle. Systemic physiology assessed throughout period. Serial serum samples obtained pre-injury, as well at 1 min, 30 h, 3 h 6 post-injury, for detailed analysis astroglial biomarker glial fibrillary acidic protein (GFAP) ubiquitin carboxy-terminal hydrolase L1 (UCH-L1). Tissue collected 6h following histological assessment diffuse axonal injury, using antibodies against amyloid precursor (APP). Animals showed significant increases circulating GFAP levels from baseline however, treatment associated with greater compared There no differences numbers APP+ swellings within pig thalamus treatment, alterations morphological properties swellings, including reduced swelling area increased roundness, observed. Additionally, expression neurite outgrowth marker, growth 43 (GAP43) suggesting effects on warrant further investigation.

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