Hypoxia-inducible factor-1α upregulation in microglia following hypoxia protects against ischemia-induced cerebral infarction

被引:36
作者
Huang, Tao [1 ]
Huang, Weiyi [2 ]
Zhang, Zhiqiang [1 ]
Yu, Lei [3 ]
Xie, Caijun [1 ]
Zhu, Dongan [1 ]
Peng, Zizhuang [1 ]
Chen, Jiehan [1 ]
机构
[1] Guangzhou Univ Chinese Med, Affiliated Hosp 2, Dept Neurosurg, Guangdong Prov Hosp Chinese Med, Guangzhou 510120, Guangdong, Peoples R China
[2] Southern Med Univ, Natl Key Clin Specialty,Zhujiang Hosp, Neurosurg Inst Guangdong Prov,Dept Neurosurg, Guangdong Prov Key Lab Brain Funct Repair & Regen, Guangzhou, Guangdong, Peoples R China
[3] Southern Med Univ, Key Lab Construct & Detect Guangdong Prov, Dept Anat, Guangzhou, Guangdong, Peoples R China
关键词
brain ischemia; hypoxia; hypoxia-inducible factor-1 alpha; isoform of nitric oxide synthase; microglia; neuroprotection; NITRIC-OXIDE SYNTHASE; NEUROPROTECTION; ACTIVATION; EXPRESSION; INJURY; REPERFUSION; PATHOLOGY; STROKE; MICE; CELL;
D O I
10.1097/WNR.0000000000000236
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Activated microglia were considered to be the toxic inflammatory mediators that induce neuron degeneration after brain ischemia. Hypoxia can enhance the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in microglia and cause microglial activation. However, intermittent hypoxia has been reported recently to be capable of protecting the body from myocardial ischemia. We established a high-altitude environment as the hypoxic condition in this study. The hypoxic condition displayed a neuroprotective effect after brain ischemia, and mice exposed to this condition presented better neurological performance and smaller infarct size. At the same time, a high level of HIF-1 alpha, low level of isoform of nitric oxide synthase, and a reduction in microglial activation were also seen in ischemic focus of hypoxic mice. However, this neuroprotective effect could be blocked by 2-methoxyestradiol, the HIF-1 alpha inhibitor. Our finding suggested that HIF-1 alpha expression was involved in microglial activation in vitro and was regulated by oxygen supply. The microglia were inactivated by re-exposure to hypoxia, which might be due to overexpression of HIF-1 alpha. These results indicated that hypoxic conditions can be exploited to achieve maximum neuroprotection after brain ischemia. This mechanism possibly lies in microglial inactivation through regulation of the expression of HIF-1 alpha. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
引用
收藏
页码:1122 / 1128
页数:7
相关论文
共 25 条
[1]  
Bal-Price A, 2001, J NEUROSCI, V21, P6480
[2]   Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-α secretion [J].
Berta, Temugin ;
Park, Chul-Kyu ;
Xu, Zhen-Zhong ;
Xie, Ruo-Gang ;
Liu, Tong ;
Lu, Ning ;
Liu, Yen-Chin ;
Ji, Ru-Rong .
JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (03) :1173-1186
[3]   Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice [J].
Cao, Can-xiang ;
Yang, Qing-wu ;
Lv, Feng-lin ;
Cu, Jie ;
Fu, Hua-bin ;
Wang, Jing-zhou .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 353 (02) :509-514
[4]   Baicalin attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-oxidative and anti-apoptotic pathways [J].
Cao, Yonggang ;
Mao, Xiaoyuan ;
Sun, Chunyan ;
Zheng, Ping ;
Gao, Jingquan ;
Wang, Xiaorui ;
Min, Dongyu ;
Sun, Hongli ;
Xie, Ni ;
Cai, Jiqun .
BRAIN RESEARCH BULLETIN, 2011, 85 (06) :396-402
[5]   MODULATION OF HUMAN MICROGLIAL CELL SUPEROXIDE PRODUCTION BY CYTOKINES [J].
CHAO, CC ;
HU, SX ;
PETERSON, PK .
JOURNAL OF LEUKOCYTE BIOLOGY, 1995, 58 (01) :65-70
[6]   NECROSTATIN-1 ATTENUATES MITOCHONDRIAL DYSFUNCTION IN NEURONS AND ASTROCYTES FOLLOWING NEONATAL HYPOXIA-ISCHEMIA [J].
Chavez-Valdez, R. ;
Martin, L. J. ;
Flock, D. L. ;
Northington, F. J. .
NEUROSCIENCE, 2012, 219 :192-203
[7]   ACTIVATION OF METABOTROPIC RECEPTORS HAS A NEUROPROTECTIVE EFFECT IN A RODENT MODEL OF FOCAL ISCHEMIA [J].
CHIAMULERA, C ;
ALBERTINI, P ;
VALERIO, E ;
REGGIANI, A .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1992, 216 (02) :335-336
[8]   MICROGLIAL AGGREGATION IN THE DENTATE GYRUS - A MARKER OF MILD HYPOXIC-ISCHEMIC BRAIN INSULT IN HUMAN INFANTS [J].
DELBIGIO, MR ;
BECKER, LE .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 1994, 20 (02) :144-151
[9]   Molecular pathology of cerebral ischemia: Delayed gene expression and strategies for neuroprotection [J].
Iadecola, C ;
Ross, ME .
FRONTIERS OF NEUROLOGY: A SYMPOSIUM IN HONOR OF FRED PLUM, 1997, 835 :203-217
[10]   Inducible nitric oxide synthase following hypoxia in rat cultured glial cells [J].
Kawase, M ;
Kinouchi, H ;
Kato, I ;
Akabane, A ;
Kondo, T ;
Arai, S ;
Fujimura, M ;
Okamoto, H ;
Yoshimoto, T .
BRAIN RESEARCH, 1996, 738 (02) :319-322