The overall objective of Core A is to provide analytical support to Projects 1, 2, and 3 and the Probe and Pharmaceutical Optimization Core (Core B). Core A is an integral part of the center by providing advanced analytical support, training, and cutting edge analytical techniques for drug and biomarker detection. More specifically, Core A will develop methods for the detection of target compounds and their metabolites by LC-MS or GC-MS and provide QC analysis of standard solutions prior to their use in projects. Detailed rodent ADME studies for the anticonvulsants and neuroprotectants will be performed to assist the center projects in dose selection. Core A will work with Project 2 in the identification of biomarkers of seizure as a biochemical test of how therapeutic efficacy. Metabolomics techniques, both targeted and global will be employed. Targeted metabolomics will focus on both oxylipins and neurosteroids since levels in both pathways are altered after a seizure. Global metabolomics, as a broader approach, can identify biomarkers of seizure and therapy if needed. Current methods of detection of tetramethylenedisulfotetramine (TETs) are insensitive. TETs seems like an ideal candidate for an immunoassay, since it has several heteroatoms to provide recognition points for the antibody. An additional benefit of immunoassay is its potential to be packaged in a field deployable platform for on-site detection. When there is a clear need, immunoassays to other toxins and their metabolites will be created. Objective-1: Provide general analytical support using GC-MS or LC-MS for the detection of toxins or drugs and their metabolites in biological matrices and formulations. Objective-2: Determine the metabolomic profiles of brain tissue from Projects 1 and 2 as biomarkers of seizure damage for use in assessing neuroprotective efficacy of candidate therapeutics. Objective-3: Develop innovative immunoassay methods for detection of TETs in biological and environmental matrices.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54NS079202-01
Application #
8411764
Study Section
Special Emphasis Panel (ZRG1-MDCN-J (54))
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
1
Fiscal Year
2012
Total Cost
$402,710
Indirect Cost
$141,210
Name
University of California Davis
Department
Type
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Lee, Kin Sing Stephen; Henriksen, Niel M; Ng, Connie J et al. (2017) Probing the orientation of inhibitor and epoxy-eicosatrienoic acid binding in the active site of soluble epoxide hydrolase. Arch Biochem Biophys 613:1-11
Wagner, Karen; Gilda, Jennifer; Yang, Jun et al. (2017) Soluble epoxide hydrolase inhibition alleviates neuropathy in Akita (Ins2 Akita) mice. Behav Brain Res 326:69-76
Hwang, Sung Hee; Wagner, Karen; Xu, Jian et al. (2017) Chemical synthesis and biological evaluation of ?-hydroxy polyunsaturated fatty acids. Bioorg Med Chem Lett 27:620-625
Nguyen, Hai M; Singh, Vikrant; Pressly, Brandon et al. (2017) Structural Insights into the Atomistic Mechanisms of Action of Small Molecule Inhibitors Targeting the KCa3.1 Channel Pore. Mol Pharmacol 91:392-402
Wagner, K; Lee, K S S; Yang, J et al. (2017) Epoxy fatty acids mediate analgesia in murine diabetic neuropathy. Eur J Pain 21:456-465
Cao, Zhengyu; Xu, Jian; Hulsizer, Susan et al. (2017) Influence of tetramethylenedisulfotetramine on synchronous calcium oscillations at distinct developmental stages of hippocampal neuronal cultures. Neurotoxicology 58:11-22
Chapman, Christopher A R; Wang, Ling; Chen, Hao et al. (2017) Nanoporous Gold Biointerfaces: Modifying Nanostructure to Control Neural Cell Coverage and Enhance Electrophysiological Recording Performance. Adv Funct Mater 27:
Hu, Pingping; Wu, Xiaojuan; Khandelwal, Alok R et al. (2017) Endothelial Nox4-based NADPH oxidase regulates atherosclerosis via soluble epoxide hydrolase. Biochim Biophys Acta 1863:1382-1391
Pressly, Brandon; Nguyen, Hai M; Wulff, Heike (2017) GABAA receptor subtype selectivity of the proconvulsant rodenticide TETS. Arch Toxicol :
Hobson, Brad A; Sisó, Sílvia; Rowland, Douglas J et al. (2017) From the Cover: MagneticResonance Imaging Reveals Progressive Brain Injury in Rats Acutely Intoxicated With Diisopropylfluorophosphate. Toxicol Sci 157:342-353

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