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 | |
dc.contributor.author | Wu, Jiangbo | |
dc.contributor.author | Lyu, Jingjun | |
dc.contributor.author | Jiang, Maorong | |
dc.contributor.author | Lu, Liping | |
dc.contributor.author | Zhu, Minghua | |
dc.contributor.author | Wang, Wei | |
dc.contributor.author | Wang, Zhuoran | |
dc.contributor.author | Liu, Qiang | |
dc.contributor.author | Hoffmann, Ulrike | |
dc.contributor.author | Karhausen, Jörn | |
dc.contributor.author | Sheng, Huaxin | |
dc.contributor.author | Zhang, Weiguo | |
dc.contributor.author | 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 | ||
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 | |
dc.subject | HPA | |
dc.subject | immune response | |
dc.subject | immunosuppression | |
dc.subject | 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 | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Anesthesiology | |
pubs.organisational-group | Clinical Science Departments | |
pubs.organisational-group | Faculty | |
pubs.organisational-group | Anesthesiology, Neuroanesthesia | |
pubs.publication-status | Published | |
pubs.volume | 41 |