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

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Date
2021-05
Authors
Zhao, Qiang
Shen, Yuntian
Li, Ran
Wu, Jiangbo
Lyu, Jingjun
Jiang, Maorong
Lu, Liping
Zhu, Minghua
Wang, Wei
Wang, Zhuoran
Liu, Qiang
Hoffmann, Ulrike
Karhausen, Jörn
Sheng, Huaxin
Zhang, Weiguo
Yang, Wei
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(16 total)
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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.
Type
Journal article
Subject
Cardiac arrest
HPA
immune response
immunosuppression
resuscitation
Permalink
https://hdl.handle.net/10161/23237
Published Version (Please cite this version)
10.1177/0271678x20948612
Publication Info
Zhao, Qiang; Shen, Yuntian; Li, Ran; Wu, Jiangbo; Lyu, Jingjun; Jiang, Maorong; ... Yang, Wei (2021). Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 41(5). pp. 1091-1102. 10.1177/0271678x20948612. Retrieved from https://hdl.handle.net/10161/23237.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Ulrike Hoffmann

Assistant Professor of Anesthesiology
Karhausen

Jorn Karhausen

Adjunct Associate Professor in the Department of Anesthesiology
Sheng

Huaxin Sheng

Associate Professor in Anesthesiology
We have successfully developed various rodent models of brain and spinal cord injuries in our lab, such as focal cerebral ischemia, global cerebral ischemia, head trauma, subarachnoid hemorrhage, intracerebral hemorrhage, spinal cord ischemia and compression injury. We also established cardiac arrest and hemorrhagic shock models for studying multiple organ dysfunction.  Our current studies focus on two projects. One is to examine the efficacy of catalytic antioxidant in treating cerebral is
Yang

Wei Yang

Associate Professor in Anesthesiology
Zhang

Weiguo Zhang

Adjunct Associate Professor in the Department of Immunology
Activation via the T-cell antigen receptor (TCR) triggers a cascade of intracellular biochemical events eventually leading to T-cell proliferation and effector functions. One of the earliest events is the activation of the Src family tyrosine kinases Fyn and Lck. The activated Src family kinases phosphorylate the CD3 subunits and TCRζ chains. ZAP-70 tyrosine kinase is recruited to the antigen receptors via the binding to CD3 and TCRζ. ZAP-70 is then tyrosine phosphorylated b
Zhu

Minghua Zhu

Assistant Research Professor of Immunology
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