Critical role of matrix metallopeptidase 9 in postoperative cognitive dysfunction and age-dependent cognitive decline

被引:44
作者
Bi, Jiangjiang [1 ,2 ]
Shan, Weiran [1 ]
Luo, Ailin [2 ]
Zuo, Zhiyi [1 ]
机构
[1] Univ Virginia, Dept Anesthesiol, Charlottesville, VA 22903 USA
[2] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Anesthesiol, Wuhan, Hubei, Peoples R China
基金
美国国家卫生研究院;
关键词
age-dependent cognitive decline; matrix metallopeptidase 9; neuroinflammation; postoperative cognitive dysfunction; BLOOD-BRAIN-BARRIER; HEMORRHAGIC TRANSFORMATION; RATS; SURGERY; METALLOPROTEINASE; NEUROINFLAMMATION; EXPRESSION; STROKE; MEMORY; THROMBOLYSIS;
D O I
10.18632/oncotarget.15545
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Postoperative cognitive dysfunction (POCD) is a significant clinical syndrome. Neuroinflammation is an important pathological process for POCD. However, it is not clear how systemic inflammation induced by surgery on peripheral tissues or organs is transmitted into the brain. We determined whether matrix metallopeptidase 9 (MMP9), a protein that can increase blood-brain barrier permeability, is critical in this transmission. The role of MMP9 in age-dependent cognitive decline was also determined. Methods: Two-month old male C57BL/6J wild-type mice and MMP9-/- mice were randomly assigned to control or surgery groups. The surgery was right carotid artery exposure under isoflurane anesthesia. Cognitive function was tested from one week after the surgery by Barnes maze and fear conditioning. Cognitive function of 2-month old C57BL/6J mice was compared with that of 18-month old mice. Results: Surgery increased the expression of interleukin 1 beta, interleukin 6 and ionized calcium binding adapter molecule 1, inflammation indicators, in the brain of the wild-type mice. Blood-brain barrier permeability was increased by surgery. Surgery also impaired the learning and memory of these mice. These surgical effects were absent in the MMP9-/- mice. Eighteen-month old wild-type mice had poorer performance in Barnes maze and fear conditioning tests and lower MMP9 protein expression and activity than did the 2-month old mice. Conclusion: MMP9 is critical for transmission of systemic inflammation into the brain for POCD. MMP9 may also play a role in age-dependent cognitive decline.
引用
收藏
页码:51817 / 51829
页数:13
相关论文
共 32 条
[1]   Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia [J].
Asahi, M ;
Wang, XY ;
Mori, T ;
Sumii, T ;
Jung, JC ;
Moskowitz, MA ;
Fini, ME ;
Lo, EH .
JOURNAL OF NEUROSCIENCE, 2001, 21 (19) :7724-7732
[2]   Apolipoprotein E controls cerebrovascular integrity via cyclophilin A [J].
Bell, Robert D. ;
Winkler, Ethan A. ;
Singh, Itender ;
Sagare, Abhay P. ;
Deane, Rashid ;
Wu, Zhenhua ;
Holtzman, David M. ;
Betsholtz, Christer ;
Armulik, Annika ;
Sallstrom, Jan ;
Berk, Bradford C. ;
Zlokovic, Berislav V. .
NATURE, 2012, 485 (7399) :512-516
[3]   Metalloproteinases and Wound Healing [J].
Caley, Matthew P. ;
Martins, Vera L. C. ;
O'Toole, Edel A. .
ADVANCES IN WOUND CARE, 2015, 4 (04) :225-234
[4]   Isoflurane Induces Learning Impairment That Is Mediated by Interleukin 1β in Rodents [J].
Cao, Lin ;
Li, Liaoliao ;
Lin, Daowei ;
Zuo, Zhiyi .
PLOS ONE, 2012, 7 (12)
[5]   Isoflurane anesthesia results in reversible ultrastructure and occludin tight junction protein expression changes in hippocampal blood-brain barrier in aged rats [J].
Cao, Yiyun ;
Ni, Cheng ;
Li, Zhengqian ;
Li, Lunxu ;
Liu, Yajie ;
Wang, Chunyi ;
Zhong, Yanfeng ;
Cui, Dehua ;
Guo, Xiangyang .
NEUROSCIENCE LETTERS, 2015, 587 :51-56
[6]   Depletion of Bone Marrow-derived Macrophages Perturbs the Innate Immune Response to Surgery and Reduces Postoperative Memory Dysfunction [J].
Degos, Vincent ;
Vacas, Susana ;
Han, Zhenying ;
van Rooijen, Nico ;
Gressens, Pierre ;
Su, Hua ;
Young, William L. ;
Maze, Mervyn .
ANESTHESIOLOGY, 2013, 118 (03) :527-536
[7]   Critical role of matrix metalloprotease-9 in chronic high fat diet-induced cerebral vascular remodelling and increase of ischaemic brain injury in mice [J].
Deng, Jiao ;
Zhang, Junfeng ;
Feng, Chenzhuo ;
Xiong, Lize ;
Zuo, Zhiyi .
CARDIOVASCULAR RESEARCH, 2014, 103 (04) :473-484
[8]   MMP9: A novel function in synaptic plasticity [J].
Dziembowska, Magdalena ;
Wlodarczyk, Jakub .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2012, 44 (05) :709-713
[9]  
Fan D, 2014, MOL NEUROBIOL
[10]   Fluorescence imaging of blood-brain barrier disruption [J].
Hawkins, BT ;
Egleton, RD .
JOURNAL OF NEUROSCIENCE METHODS, 2006, 151 (02) :262-267