title: Brain redox imaging in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe.
abstract: Much evidence supports the idea that oxidative stress is involved in the pathogenesis of epilepsy, and therapeutic interventions with antioxidants are expected as adjunct antiepileptic therapy. The aims of this study were to non-invasively obtain spatially resolved redox data from control and pentylenetetrazole (PTZ)-induced kindled mouse brains by electron paramagnetic resonance (EPR) imaging and to visualize the brain regions that are sensitive to oxidative damage. After infusion of the redox-sensitive imaging probe 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), a series of EPR images of PTZ-induced mouse heads were measured. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of redox status in vivo and mapped as a redox map. The obtained redox map showed heterogeneity in the redox status in PTZ-induced mouse brains compared with control. The co-registered image of the redox map and magnetic resonance imaging (MRI) for both control and PTZ-induced mice showed a clear change in the redox status around the hippocampus after PTZ. To examine the role of antioxidants on the brain redox status, the levels of antioxidants were measured in brain tissues of control and PTZ-induced mice. Significantly lower concentrations of glutathione in the hippocampus of PTZ-kindled mice were detected compared with control. From the results of both EPR imaging and the biochemical assay, the hippocampus was found to be susceptible to oxidative damage in the PTZ-induced animal model of epilepsy.
authors.affiliation: Center for Medical Education, Sapporo Medical University, Sapporo, Hokkaido, Japan.
authors.forename: Miho C
authors.initials: MC
authors.lastname: Emoto
authors.affiliation: Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yamato
authors.affiliation: Department of Systems Innovation, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Sato-Akaba
authors.affiliation: Department of Bio-functional Science, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan 　; JST, PRESTO, Kawaguchi, Saitama, Japan
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Center for Medical Education, Sapporo Medical University, Sapporo, Hokkaido, Japan. Electronic address: hgfujii@sapmed.ac.jp.
authors.forename: Hirotada G
authors.initials: HG
authors.lastname: Fujii
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007696:Kindling, Neurologic; D008297:Male; D008810:Mice, Inbred C57BL; D009589:Nitrogen Oxides / Q000378:metabolism*; D010084:Oxidation-Reduction; D010433:Pentylenetetrazole
chemical_list: C585850:3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D005978:Glutathione; C039900:nitroxyl; D001205:Ascorbic Acid; D010433:Pentylenetetrazole
keywords: EPR; Epilepsy; Hippocampus; In vivo imaging; MRI; Oxidative stress; Redox state