Abstracts

Rationale: Goal of this study was to identify unique plasma metabolites in an animal model of Temporal Lobe Epilepsy (TLE) using mass spectrometry-based metabolomics which can offer invaluable insights into the etiology of TLE and suggest biomarkers that predict its onset and/or severity. Methods: The kainic acid (KA) model of TLE was used in this study. Plasma metabolites were measured in rat plasma collected at acute (48h), latent (7d), and chronic (12wk) stages of epileptogenesis (n=3-5). Samples were extracted using the Bligh-Dyer extraction method with methyl-tert-butyl ether and water. The hydrophilic and hydrophobic fractions were analyzed by High Performance Liquid Chromatography-Mass Spectrometry (Agilent Technologies 6510 Q-TOF LC/MS and Agilent Technologies 6210 Time-of-flight LC/MS, respectively). Statistical and fold-change analysis change (p<0.05, >1.5-fold change) was performed using Agilent Technologies Mass Profiler Professional. Metabolites were tentatively identified using exact mass and isotope ratios. Results: Outstanding are changes in vitamin D derivatives, which have been shown to play a role in epilepsy. Unique vitamin D metabolites were changed in plasma at all time points. Especially in the lipid fraction of plasma of chronically epileptic rats vitamin D derivatives were decreased. Other changes in vitamin D metabolites were observed in rat plasma after 48h (acute) and 1wk (latent period). Additional metabolites of biomarker potential are phospholipids as well as di- and triglycerols composed of polyunsaturated fatty acids, which have anticonvulsant properties. Phosphatidylcholines, phosphoethanolamines, ceramides, and di-and triglycerols are the most prominently changed compound classes in plasma of chronically epileptic rats. Conclusions: A metabolomics approach can uncover mechanisms of epileptogenesis in TLE and aid biomarker discovery. Our data demonstrates that we can assess biomarkers in rat plasma relevant to epileptogenesis and TLE. Funding: CURE Infantile Spasms Initiative (MP), 1R01NS086423-01 (MP)