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

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A Correction to this article was published on 31 August 2018

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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.

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Change history

  • 31 August 2018

    The order of corresponding author was inadvertently published. Hence, the first and the second corresponding authors should be Min Zhang (hebmuzhangmin@163.com) and Jing-Ge Zhang (zhangjg001@163.com).

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

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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).

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Author notes

  1. Ya-Jie Huang, Yu-Jia Yuan, and Yi-Xian Liu have contributed equally to this work.

Authors and Affiliations

  1. Undergraduate of Clinical Medicine, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China

    Ya-Jie Huang, Yu-Jia Yuan, Meng-Yue Zhang & Tian-Ci Wang

  2. Department of Physiology, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China

    Yi-Xian Liu

  3. Department of Pathophysiology, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, Hebei, People’s Republic of China

    Jing-Ge Zhang, Li-Nan Zhang, Yu-Yan Hu, Xiao-Hui Xian, Jie Qi & Min Zhang

  4. Department of Science and Technology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000, People’s Republic of China

    Li Li

  5. Aging and Cognition Neuroscience Laboratory of Hebei Province, Shijiazhuang, 050017, People’s Republic of China

    Min Zhang

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  1. Ya-Jie Huang
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Correspondence to Jing-Ge Zhang or Min Zhang.

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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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Huang, YJ., Yuan, YJ., Liu, YX. et al. Nitric Oxide Participates in the Brain Ischemic Tolerance Induced by Intermittent Hypobaric Hypoxia in the Hippocampal CA1 Subfield in Rats. Neurochem Res 43, 1779–1790 (2018). https://doi.org/10.1007/s11064-018-2593-9

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