Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.
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.
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https://hdl.handle.net/10161/23237Published Version (Please cite this version)
10.1177/0271678x20948612Publication 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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Show full item recordScholars@Duke
Ulrike Hoffmann
Assistant Professor of Anesthesiology
Jorn Karhausen
Adjunct Associate Professor in the Department of Anesthesiology
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
Wei Yang
Associate Professor in Anesthesiology
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
Minghua Zhu
Assistant Research Professor of Immunology
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