Orexin-A inhibits cerebral ischaemic inflammatory injury mediated by the nuclear factor-KB signalling pathway and alleviates stroke-induced immunodepression in mice

被引：5

作者：

Zhao, Dong ^{[1
]}

Zeng, Zhaofu ^{[1
]}

Mo, Huaheng ^{[1
]}

Hu, Weihua ^{[1
]}

Tian, Sumei ^{[1
]}

Hu, Die ^{[1
]}

Gong, Lin ^{[1
]}

Hu, Ke ^{[1
]}

机构：

[1] Renmin Hosp Wuhan Univ, Dept Resp & Crit Care Med, Zhangzhidong Rd 99, Wuhan 430060, Peoples R China

来源：

BRAIN RESEARCH BULLETIN | 2021年 / 174卷

基金：

中国国家自然科学基金;

关键词：

Orexin-A; Cerebral ischaemic inflammatory injury; Nuclear factor-KB signalling pathway; Stroke-induced immunodepression; ARTERY OCCLUSION; SPLENIC ATROPHY; PNEUMONIA; SYSTEM; INFECTIONS; NEURONS; RATS;

D O I：

10.1016/j.brainresbull.2021.06.021

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Cerebral ischaemia is accompanied by infectious complications due to immunosuppression, known as strokeinduced immunodepression (SIID). Orexin-A (OXA), a neuropeptide produced in the hypothalamus, has been reported to have neuroprotective properties after stroke and is known to modulate inflammatory processes in peripheral tissues. The aim of this study was to determine the effects of orexin-A (OXA) on cerebral ischaemic inflammatory injury and SIID following experimental stroke. Cerebral ischaemia was induced in C57/BL6 mice by middle cerebral artery occlusion (MCAO). A mouse model of pneumonia and poststroke pneumococcal pneumonia was established by intratracheal inoculation with S. pneumoniae in a normal mouse or MCAO mouse model on the third day. We found that OXA postconditioning inhibited cerebral ischaemic inflammatory injury. The mechanism involved downregulation of the NF-KB signalling pathway. In addition, OXA may serve as a potential treatment target for attenuating stroke-induced immunodepression in mice.

引用

页码：296 / 304

页数：9

共 36 条

[1] Lateral hypothalamic orexin/hypocretin neurons: A role in reward-seeking and addiction [J].

Aston-Jones, Gary ;

Smith, Rachel J. ;

Sartor, Gregory C. ;

Moorman, David E. ;

Massi, Lema ;

Tahsili-Fahadan, Pouya ;

Richardson, Kimberlei A. .

BRAIN RESEARCH, 2010, 1314 :74-90

[2] The immunology of acute stroke [J].

Chamorro, Angel ;

Meisel, Andreas ;

Planas, Anna M. ;

Urra, Xabier ;

van de Beek, Diederik ;

Veltkamp, Roland .

NATURE REVIEWS NEUROLOGY, 2012, 8 (07) :401-410

[3] Immunomodulatory treatment with systemic GM-CSF augments pulmonary immune responses and improves neurological outcome after experimental stroke [J].

Dames, Claudia ;

Winek, Katarzyna ;

Beckers, Yasmin ;

Engel, Odilo ;

Meisel, Andreas ;

Meisel, Christian .

JOURNAL OF NEUROIMMUNOLOGY, 2018, 321 :144-149

[4] The hypocretins and sleep [J].

de Lecea, L ;

Sutcliffe, JG .

FEBS JOURNAL, 2005, 272 (22) :5675-5688

[5] Proliferating resident microglia after focal cerebral ischaemia in mice [J].

Denes, Adam ;

Vidyasagar, Rishma ;

Feng, Jianghua ;

Narvainen, Johanna ;

McColl, Barry W. ;

Kauppinen, Risto A. ;

Allan, Stuart M. .

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2007, 27 (12) :1941-1953

[6] Role of orexin A signaling in dietary palmitic acid-activated microglial cells [J].

Duffy, Cayla M. ;

Yuan, Ce ;

Wisdorf, Lauren E. ;

Billington, Charles J. ;

Kotz, Catherine M. ;

Nixon, Joshua P. ;

Butterick, Tammy A. .

NEUROSCIENCE LETTERS, 2015, 606 :140-144

[7] Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study [J].

Hoffmann, Sarah ;

Harms, Hendrik ;

Ulm, Lena ;

Nabavi, Darius G. ;

Mackert, Bruno-Marcel ;

Schmehl, Ingo ;

Jungehulsing, Gerhard J. ;

Montaner, Joan ;

Bustamante, Alejandro ;

Hermans, Marcella ;

Hamilton, Frank ;

Goehler, Jos ;

Malzahn, Uwe ;

Malsch, Carolin ;

Heuschmann, Peter U. ;

Meisel, Christian ;

Meisel, Andreas .

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2017, 37 (12) :3671-3682

[8] Infarct Volume is a Major Determiner of Post-Stroke Immune Cell Function and Susceptibility to Infection [J].

Hug, Andreas ;

Dalpke, Alexander ;

Wieczorek, Nina ;

Giese, Thomas ;

Lorenz, Alexander ;

Auffarth, Gerd ;

Liesz, Arthur ;

Veltkamp, Roland .

STROKE, 2009, 40 (10) :3226-3232

[9] Simvastatin Attenuates Stroke-induced Splenic Atrophy and Lung Susceptibility to Spontaneous Bacterial Infection in Mice [J].

Jin, Rong ;

Zhu, Xiaolei ;

Liu, Lin ;

Nanda, Anil ;

Granger, D. Neil ;

Li, Guohong .

STROKE, 2013, 44 (04) :1135-+

[10] Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial [J].

Kalra, Lalit ;

Irshad, Saddif ;

Hodsoll, John ;

Simpson, Matthew ;

Gulliford, Martin ;

Smithard, David ;

Patel, Anita ;

Rebollo-Mesa, Irene .

LANCET, 2015, 386 (10006) :1835-1844

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