Brain redox imaging in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe

Miho C. Emoto, Mayumi Yamato, Hideo Sato-Akaba, Ken-Ichi Yamada, Hirotada G. Fujii

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)40-44
Number of pages5
JournalNeuroscience Letters
Volume608
DOIs
Publication statusPublished - Nov 3 2015

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Pentylenetetrazole
Electron Spin Resonance Spectroscopy
Neuroimaging
Oxidation-Reduction
Epilepsy
Brain
Hippocampus
Antioxidants
Head
Anticonvulsants
Glutathione
Oxidative Stress
Animal Models
Pharmacokinetics
Magnetic Resonance Imaging

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Brain redox imaging in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe. / Emoto, Miho C.; Yamato, Mayumi; Sato-Akaba, Hideo; Yamada, Ken-Ichi; Fujii, Hirotada G.

In: Neuroscience Letters, Vol. 608, 03.11.2015, p. 40-44.

Research output: Contribution to journalArticle

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