title: Exploratory Metabolomics Profiling in the Kainic Acid Rat Model Reveals Depletion of 25-Hydroxyvitamin D3 during Epileptogenesis.
abstract: Currently, no reliable markers are available to evaluate the epileptogenic potential of a brain injury. The electroencephalogram is the standard method of diagnosis of epilepsy; however, it is not used to predict the risk of developing epilepsy. Biomarkers that indicate an individual's risk to develop epilepsy, especially those measurable in the periphery are urgently needed. Temporal lobe epilepsy (TLE), the most common form of acquired epilepsy, is characterized by spontaneous recurrent seizures following brain injury and a seizure-free "latent" period. Elucidation of mechanisms at play during epilepsy development (epileptogenesis) in animal models of TLE could enable the identification of predictive biomarkers. Our pilot study using liquid chromatography-mass spectrometry metabolomics analysis revealed changes (p-value ≤ 0.05, ≥1.5-fold change) in lipid, purine, and sterol metabolism in rat plasma and hippocampus during epileptogenesis and chronic epilepsy in the kainic acid model of TLE. Notably, disease development was associated with dysregulation of vitamin D3 metabolism at all stages and plasma 25-hydroxyvitamin D3 depletion in the acute and latent phase of injury-induced epileptogenesis. These data suggest that plasma VD3 metabolites reflect the severity of an epileptogenic insult and that a panel of plasma VD3 metabolites may be able to serve as a marker of epileptogenesis.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado, School of Pharmacy, 12850 East Montview Boulevard, Aurora, CO 80045, USA.|Department of Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Svenja
authors.initials: S
authors.lastname: Heischmann
authors.affiliation: Department of Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Quinn
authors.affiliation: Department of Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Charmion
authors.initials: C
authors.lastname: Cruickshank-Quinn
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado, School of Pharmacy, 12850 East Montview Boulevard, Aurora, CO 80045, USA.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Liang
authors.affiliation: Department of Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Rick
authors.initials: R
authors.lastname: Reisdorph
authors.affiliation: Department of Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Nichole
authors.initials: N
authors.lastname: Reisdorph
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado, School of Pharmacy, 12850 East Montview Boulevard, Aurora, CO 80045, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Patel
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002112:Calcifediol / Q000097:blood*; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced* / Q000473:pathology*; D006624:Hippocampus / Q000737:chemistry*; D007608:Kainic Acid / Q000008:administration & dosage*; D013058:Mass Spectrometry; D055432:Metabolomics; D010865:Pilot Projects; D010949:Plasma / Q000737:chemistry; D051381:Rats
chemical_list: D015415:Biomarkers; D002112:Calcifediol; D007608:Kainic Acid