Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.

dc.contributor.author

Zhao, Qiang

dc.contributor.author

Shen, Yuntian

dc.contributor.author

Li, Ran

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Wu, Jiangbo

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Lyu, Jingjun

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Jiang, Maorong

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Lu, Liping

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Zhu, Minghua

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Wang, Wei

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Wang, Zhuoran

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Liu, Qiang

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Hoffmann, Ulrike

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Karhausen, Jörn

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Sheng, Huaxin

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Zhang, Weiguo

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Yang, Wei

dc.date.accessioned

2021-06-01T13:40:37Z

dc.date.available

2021-06-01T13:40:37Z

dc.date.issued

2021-05

dc.date.updated

2021-06-01T13:40:36Z

dc.description.abstract

In patients who are successfully resuscitated after initial cardiac arrest (CA), mortality and morbidity rates are high, due to ischemia/reperfusion injury to the whole body including the nervous and immune systems. How the interactions between these two critical systems contribute to post-CA outcome remains largely unknown. Using a mouse model of CA and cardiopulmonary resuscitation (CA/CPR), we demonstrate that CA/CPR induced neuroinflammation in the brain, in particular, a marked increase in pro-inflammatory cytokines, which subsequently activated the hypothalamic-pituitary-adrenal (HPA) axis. Importantly, this activation was associated with a severe immunosuppression phenotype after CA. The phenotype was characterized by a striking reduction in size of lymphoid organs accompanied by a massive loss of immune cells and reduced immune function of splenic lymphocytes. The mechanistic link between post-CA immunosuppression and the HPA axis was substantiated, as we discovered that glucocorticoid treatment, which mimics effects of the activated HPA axis, exacerbated post-CA immunosuppression, while RU486 treatment, which suppresses its effects, significantly mitigated lymphopenia and lymphoid organ atrophy and improved CA outcome. Taken together, targeting the HPA axis could be a viable immunomodulatory therapeutic to preserve immune homeostasis after CA/CPR and thus improve prognosis of post-resuscitation CA patients.

dc.identifier.issn

0271-678X

dc.identifier.issn

1559-7016

dc.identifier.uri

https://hdl.handle.net/10161/23237

dc.language

eng

dc.publisher

SAGE Publications

dc.relation.ispartof

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

dc.relation.isversionof

10.1177/0271678x20948612

dc.subject

Cardiac arrest

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HPA

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immune response

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immunosuppression

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resuscitation

dc.title

Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.

dc.type

Journal article

duke.contributor.orcid

Sheng, Huaxin|0000-0002-4325-2940

duke.contributor.orcid

Yang, Wei|0000-0001-5719-4393

pubs.begin-page

1091

pubs.end-page

1102

pubs.issue

5

pubs.organisational-group

School of Medicine

pubs.organisational-group

Anesthesiology, Cardiothoracic

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Duke

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Anesthesiology

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Clinical Science Departments

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Faculty

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Anesthesiology, Neuroanesthesia

pubs.publication-status

Published

pubs.volume

41

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