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Neurochemical Research

, Volume 43, Issue 7, pp 1464–1475 | Cite as

Increased Superoxide Dismutase 2 by Allopregnanolone Ameliorates ROS-Mediated Neuronal Death in Mice with Pilocarpine-Induced Status Epilepticus

  • Inja Cho
  • Won-Joo Kim
  • Hyun-Woo Kim
  • Kyoung Heo
  • Byung In Lee
  • Yang-Je ChoEmail author
Original Paper
  • 234 Downloads

Abstract

Excessive production of reactive oxygen species (ROS), along with dysfunction of the antioxidant defense system, such as that involving superoxide dismutase (SOD), may play a major role in neuronal death following status epilepticus (SE). Neurosteroids, which are allosteric modulators of the GABAA receptor in cerebral metabolism, have been suggested as being neuroprotective in various animal models; however, their effect to preventing ROS has not been examined. Herein, we investigate the neuroprotective role of allopregnanolone, the prototypical neurosteroid in the brain, in relation to the ROS-mediated neuronal injury. Adult male C57BL/6 mice were subjected to SE and treated with allopregnanolone. Hippocampal cell death was assessed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and ROS production was investigated by in situ detection of oxidized hydroethidine. SOD2 expression was analyzed by both western blot and immunofluorescent staining in the hippocampal subfields. In mice treated with allopregnanolone after SE, hippocampal cell death, DNA fragmentation, oxidative DNA damage, and ROS production were reduced significantly compared to mice subjected to vehicle treatment after SE. Hippocampal SOD2 expression was significantly increased by allopregnanolone. These finding suggest that allopregnanolone plays a neuroprotective role, with not only anticonvulsant but also antioxidant effects, by increasing SOD2 in pilocarpine-induced SE model.

Keywords

Status epilepticus Oxidative stress Superoxide dismutase Hippocampus Allopregnanolone 

Notes

Acknowledgements

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2015R1D1A1A01059901).

Supplementary material

11064_2018_2561_MOESM1_ESM.docx (150 kb)
Supplementary material 1 (DOCX 150 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurology and Epilepsy Research InstituteYonsei University College of MedicineSeoulRepublic of Korea
  2. 2.Brain Korea 21 PLUS Project for Medical ScienceYonsei UniversitySeoulRepublic of Korea
  3. 3.Department of NeurologyInje University, Haeundae Paik HospitalBusanRepublic of Korea

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