Cardiac arrest and cardiopulmonary resuscitation dysregulates the hypothalamic-pituitary-adrenal axis

Gretchen N. Neigh, Kate Karelina, Ning Zhang, Erica R. Glasper, Michael J. Owens, Paul M. Plotsky, Charles B. Nemeroff, A. Courtney Devries

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Cardiac arrest and cardiopulmonary resuscitation (CA/CPR) increase the risk for affective disorders in human survivors. Postischemic anxiety- and depressive-like behaviors have been documented in animal models of CA/CPR; however, the stability of post-CA/CPR anxiety-like behavior over time and the underlying physiologic mechanisms remain unknown. The hypothalamic-pituitary- adrenal (HPA) axis and the corticotropin releasing factor (CRF) system may mediate the pathophysiology of anxiety and depression; therefore, this study measured CA/CPR-induced changes in CRF receptor binding and HPA axis negative feedback. Mice were exposed to CA/CPR or SHAM surgery and assessed 7 or 21 days later. Consistent with earlier demonstrations of anxiety-like behavior 7 days after CA/CPR, increased anxiety-like behavior in the open field was also present 21 days after CA/CPR. On postoperative day 7, CA/CPR was associated with an increase in basal serum corticosterone concentration relative to SHAM, but this difference resolved by postoperative day 21. The Dexamethasone Suppression Test showed that the CA/CPR group had enhanced negative feedback compared with SHAM controls at postoperative day 21. Furthermore, there was a gradual increase in CRF 1 receptor binding in the paraventricular nucleus of the hypothalamus and bed nucleus of the stria terminalis, as well as a transient decrease of both CRF 1 and CRF 2A receptors in the dorsal hippocampus. Therefore, sustained changes in activity of the HPA axis and the CRF system after CA/CPR may contribute to the postischemic increase in affective disorders.

Original languageEnglish (US)
Pages (from-to)1673-1682
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number10
StatePublished - Oct 2009
Externally publishedYes


  • Cardiac arrest
  • Corticosterone
  • CRF
  • Dexamethasone
  • HPA
  • Ischemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology


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