中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (9): 1458-1464.doi: 10.4103/1673-5374.215256

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

高热对短暂性全脑缺血沙鼠海马神经元损害:与钙结合蛋白-D 28k免疫反应减弱有关?

  

  • 收稿日期:2017-07-17 出版日期:2017-09-15 发布日期:2017-09-15
  • 基金资助:

    韩国政府NRF生物医学技术发展项目;韩国科学,ICT,未来计划部机制研究项目

Effect of hyperthermia on calbindin-D 28k immunoreactivity in the hippocampal formation following transient global cerebral ischemia in gerbils

Jae-Chul Lee1, Jeong-Hwi Cho1, Tae-Kyeong Lee1, In Hye Kim1, Moo-Ho Won1, Geum-Sil Cho2, Bich-Na Shin3, In Koo Hwang4, Joon Ha Park5, Ji Hyeon Ahn5, Il Jun Kang6, Young Joo Lee7, Yang Hee Kim8   

  1. 1 Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea
    2 Department of Pharmacology & Toxicology, Shinpoong Pharmaceutical Co., Ltd., Ansan, South Korea
    3 Department of Physiology, College of Medicine, Hallym University, Chuncheon, South Korea
    4 Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National
    University, Seoul, South Korea
    5 Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, South Korea
    6 Department of Food Science and Nutrition, Hallym University, Chuncheon, South Korea
    7 Department of Emergency Medicine, Seoul Hospital, College of Medicine, Sooncheonhyang University, Seoul, South Korea
    8 Department of Surgery, School of Medicine, Kangwon National University, Chuncheon, South Korea
  • Received:2017-07-17 Online:2017-09-15 Published:2017-09-15
  • Contact: Moo-Ho Won, D.V.M., Ph.D. or Yang Hee Kim, M.D.,mhwon@kangwon.ac.kr or kyh1524@kangwon.ac.kr.
  • Supported by:

    This study was supported by the Biomedical Technology Development Program of the NRF funded by the Korean Government, MSIP (NRF-2015M3A9B6066835), and by the Bio-Synergy Research Project (NRF-2015M3A9C4076322) of the Ministry of Science, ICT and Future Planning through the National Research Foundation.

摘要:

钙结合蛋白D-28K(CB)可维持Ca2+体内平衡和保护损伤神经元。然而,我们对高热条件下,大脑中钙结合蛋白D-28K的作用知之甚少。为此实验联合应用神经细胞核抗原/钙结合蛋白D-28K免疫组织化学染色及Fluoro-Jade B组织荧光染色方法检测了高热条件对短暂性全脑缺血沙鼠海马钙结合蛋白D-28K免疫反应和神经元损害的影响。实验在短暂性脑缺血前30min和期间进行(39.5±0.2oC)的高热干预。随着缺血后时间的延长,高热使脑缺血沙鼠海马CA1-3区锥体细胞层和齿状回多形细胞层神经元损伤/死亡越发广泛和严重;同时,高热还明显降低了脑缺血沙鼠海马损伤或死亡神经元中钙结合蛋白D-28K免疫反应。实验结果表明,沙鼠海马钙结合蛋白D-28K免疫反应的减弱可能与海马各亚区神经元损伤/死亡的随时间变化有关。

orcid:0000-0002-7178-6501(Moo-Ho Won)
0000-0002-2754-6412(Yang Hee Kim)

关键词: 神经再生, 高热, 全脑缺血, 海马, 延迟神经元死亡, 钙结合蛋白D-28K

Abstract:

Calbindin D-28K (CB), a Ca2+-binding protein, maintains Ca2+ homeostasis and protects neurons against various insults. Hyperthermia can exacerbate brain damage produced by ischemic insults. However, little is reported about the role of CB in the brain under hyperthermic condition during ischemic insults. We investigated the effects of transient global cerebral ischemia on CB immunoreactivity as well as neuronal damage in the hippocampal formation under hyperthermic condition using immunohistochemistry for neuronal nuclei (NeuN) and CB, and Fluoro-Jade B histofluorescence staining in gerbils. Hyperthermia (39.5 ± 0.2°C) was induced for 30 minutes before and during transient ischemia. Hyperthermic ischemia resulted in neuronal damage/death in the pyramidal layer of CA1–3 area and in the polymorphic layer of the dentate gyrus at 1, 2, 5 days after ischemia. In addition, hyperthermic ischemia significantly decreaced CB immunoreactivity in damaged or dying neurons at 1, 2, 5 days after ischemia. In brief, hyperthermic condition produced more extensive and severer neuronal damage/death, and reduced CB immunoreactivity in the hippocampus following transient global cerebral ischemia. Present findings indicate that the degree of reduced CB immunoreactivity might be related with various neuronal damage/death overtime and corresponding areas after ischemic insults.

Key words: nerve regeneration, hyperthermic condition, ischemia/reperfusion injury, subregions of hippocampus, delayed neuronal death, calbindin D-28k, neural regeneration