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Neurochemical Research

, Volume 43, Issue 9, pp 1779–1790 | Cite as

Nitric Oxide Participates in the Brain Ischemic Tolerance Induced by Intermittent Hypobaric Hypoxia in the Hippocampal CA1 Subfield in Rats

  • Ya-Jie Huang
  • Yu-Jia Yuan
  • Yi-Xian Liu
  • Meng-Yue Zhang
  • Jing-Ge Zhang
  • Tian-Ci Wang
  • Li-Nan Zhang
  • Yu-Yan Hu
  • Li Li
  • Xiao-Hui Xian
  • Jie Qi
  • Min Zhang
Original Paper

Abstract

Previous studies have shown that intermittent hypobaric hypoxia (IH) preconditioning protected neurons survival from brain ischemia. However, the mechanism remains to be elucidated. The present study explored the role of nitric oxide (NO) in the process by measuring the expression of NO synthase (NOS) and NO levels. Male Wistar rats (100) were randomly assigned into four groups: sham group, IH + sham group, ischemia group and IH + ischemia group. Rats for IH preconditioning were exposed to hypobaric hypoxia mimicking 5000 m high-altitude (PB = 404 mmHg, PO2 = 84 mmHg) 6 h/day, once daily for 28 days. Global brain ischemia was established by four-vessel occlusion that has been created by Pulsinelli. Rats were sacrificed at 7th day after the ischemia for neuropathological evaluation by thionin stain. In addition, the expression of neuronal NOS (nNOS), inducible NOS (iNOS), and NO content in the hippocampal CA1 subfield were measured at 2nd day and 7th day after the ischemia. Results revealed that global brain ischemia engendered delayed neuronal death (DND), both nNOS and iNOS expression up-regulated, and NO content increased in the hippocampal CA1 subfield. IH preconditioning reduced neuronal injury induced by the ischemia, and prevented the up-regulation of NOS expression and NO production. In addition, l-NAME + ischemia group was designed to detect whether depressing NO production could alleviate the DND. Pre-administration of l-NAME alleviated DND induced by the ischemia. These results suggest that IH preconditioning plays a protective role by inhibiting the over expression of NOS and NO content after brain ischemia.

Keywords

Intermittent hypobaric hypoxia Global brain ischemia Nitric oxide synthase Nitric oxide Hippocampal CA1 subfield 

Abbreviations

BCCAs

Bilateral common carotid arteries

DND

Delayed neuronal death

EEG

Electroencephalogram

HG

Histological grade

IH

Intermittent hypobaric hypoxia

iNOS

Inducible nitric oxide synthase

l-NAME

N-nitro-l-arginine methyl ester

ND

Neuronal density

NO

Nitric oxide

NOS

Nitric oxide synthase

nNOS

Neuronal nitric oxide synthase

PBS

Phosphate-buffered saline

SD

Standard devariance

Notes

Acknowledgements

The present study was supported by the National Natural Science Foundation of China (Nos. 81771253, 31271149 and 81271454), Natural Science Foundation of Hebei Province, China (No. H2015206492) and College Students’ innovation experiment program (USIP201503A).

Compliance with Ethical Standards

Conflict of interest

We declare no conflicts of interest in this study.

Ethical Approval

All procedures performed in studies involving animals were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Laboratory Animal Care of Hebei Medical University.

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Copyright information

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

Authors and Affiliations

  • Ya-Jie Huang
    • 1
  • Yu-Jia Yuan
    • 1
  • Yi-Xian Liu
    • 2
  • Meng-Yue Zhang
    • 1
  • Jing-Ge Zhang
    • 3
  • Tian-Ci Wang
    • 1
  • Li-Nan Zhang
    • 3
  • Yu-Yan Hu
    • 3
  • Li Li
    • 4
  • Xiao-Hui Xian
    • 3
  • Jie Qi
    • 3
  • Min Zhang
    • 3
    • 5
  1. 1.Undergraduate of Clinical MedicineHebei Medical UniversityShijiazhuangPeople’s Republic of China
  2. 2.Department of PhysiologyHebei Medical UniversityShijiazhuangPeople’s Republic of China
  3. 3.Department of PathophysiologyHebei Medical UniversityShijiazhuangPeople’s Republic of China
  4. 4.Department of Science and TechnologyThe Second Hospital of Hebei Medical UniversityShijiazhuangPeople’s Republic of China
  5. 5.Aging and Cognition Neuroscience Laboratory of Hebei ProvinceShijiazhuangPeople’s Republic of China

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