Neuroprotective effects of sevoflurane against electromagnetic pulse-induced brain injury through inhibition of neuronal oxidative stress and apoptosis

Bin Deng; Hao Xu; Jin Zhang; Jin Wang; Li-Chun Han; Li-Ya Li; Guang-Li Wu; Yan-Ning Hou; Guo-Zhen Guo; Qiang Wang; Han-Fei Sang; Li-Xian Xu

doi:10.1371/journal.pone.0091019

Neuroprotective effects of sevoflurane against electromagnetic pulse-induced brain injury through inhibition of neuronal oxidative stress and apoptosis

PLoS One. 2014 Mar 10;9(3):e91019. doi: 10.1371/journal.pone.0091019. eCollection 2014.

Authors

Bin Deng¹, Hao Xu², Jin Zhang¹, Jin Wang³, Li-Chun Han⁴, Li-Ya Li⁵, Guang-Li Wu⁶, Yan-Ning Hou⁷, Guo-Zhen Guo³, Qiang Wang⁵, Han-Fei Sang⁸, Li-Xian Xu¹

Affiliations

¹ State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
² Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, the Fourth Military Medical University, Xi'an, China.
³ Department of Radiation Medicine, Faculty of Preventive Medicine, the Fourth Military Medical University, Xi'an, China.
⁴ Department of Anesthesiology, Shannxi Tumor Hospital, Xi'an, China.
⁵ Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
⁶ Department of Nephrology, Bethune International Peace Hospital of People?'s Liberation Army, Shijiazhuang, China.
⁷ Department of Clinical Pharmacology, Bethune International Peace Hospital of People's Liberation Army, Shijiazhuang, China.
⁸ Department of Clinical Pharmacology, Bethune International Peace Hospital of People's Liberation Army, Shijiazhuang, China; Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

Abstract

Electromagnetic pulse (EMP) causes central nervous system damage and neurobehavioral disorders, and sevoflurane protects the brain from ischemic injury. We investigated the effects of sevoflurane on EMP-induced brain injury. Rats were exposed to EMP and immediately treated with sevoflurane. The protective effects of sevoflurane were assessed by Nissl staining, Fluoro-Jade C staining and electron microscopy. The neurobehavioral effects were assessed using the open-field test and the Morris water maze. Finally, primary cerebral cortical neurons were exposed to EMP and incubated with different concentration of sevoflurane. The cellular viability, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assayed. TUNEL staining was performed, and the expression of apoptotic markers was determined. The cerebral cortexes of EMP-exposed rats presented neuronal abnormalities. Sevoflurane alleviated these effects, as well as the learning and memory deficits caused by EMP exposure. In vitro, cell viability was reduced and LDH release was increased after EMP exposure; treatment with sevoflurane ameliorated these effects. Additionally, sevoflurane increased SOD activity, decreased MDA levels and alleviated neuronal apoptosis by regulating the expression of cleaved caspase-3, Bax and Bcl-2. These findings demonstrate that Sevoflurane conferred neuroprotective effects against EMP radiation-induced brain damage by inhibiting neuronal oxidative stress and apoptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Behavior, Animal / drug effects
Brain Injuries / complications
Brain Injuries / drug therapy
Brain Injuries / pathology*
Caspase 3 / metabolism
Cell Survival / drug effects
Cerebral Cortex / pathology
Cognition / drug effects
Electromagnetic Fields*
L-Lactate Dehydrogenase / metabolism
Male
Malondialdehyde / metabolism
Methyl Ethers / pharmacology*
Methyl Ethers / therapeutic use
Nerve Degeneration / complications
Nerve Degeneration / drug therapy
Nerve Degeneration / pathology
Neurons / drug effects
Neurons / enzymology
Neurons / pathology*
Neurons / ultrastructure
Neuroprotective Agents / pharmacology*
Oxidative Stress / drug effects*
Rats, Sprague-Dawley
Sevoflurane
Superoxide Dismutase / metabolism
bcl-2-Associated X Protein / metabolism

Substances

Methyl Ethers
Neuroprotective Agents
bcl-2-Associated X Protein
Sevoflurane
Malondialdehyde
L-Lactate Dehydrogenase
Superoxide Dismutase
Caspase 3

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grants No. 30371763, No. 81071060, No. 81070997, No. 31100785 and No. 81171237), the Natural Science Foundation of Shaanxi Province (Grants No. 2006C254, No. 2011KJXX67 and No. 2013JM4040, 2012KTCG01-02,2013KTZB03-03), and the Fourth Military Medical University Foundation (Grant No. 2013-D03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.