title: Anxiety after cardiac arrest/cardiopulmonary resuscitation: exacerbated by stress and prevented by minocycline.
abstract: OBJECTIVE
  Stress is an important risk factor for cardiovascular disease; however, most of the research on this topic has focused on incidence rather than outcome. The goal of this study was to determine the effects of prior exposure to chronic stress on ischemia-induced neuronal death, microglial activation, and anxiety-like behavior.
  
  
  METHODS
  In Experiment 1, mice were exposed to 3 weeks of daily restraint (3 hours) and then subjected to either 8 minutes of cardiac arrest/cardiopulmonary resuscitation (CA/CPR) or sham surgery. Anxiety-like behavior, microglial activation, and neuronal damage were assessed on postischemic Day 4. In Experiment 2, mice were infused intracerebroventricularly with minocycline (10 microg/day) to determine the effect of inhibiting post-CA/CPR microglial activation on the development of anxiety-like behavior and neuronal death.
  
  
  RESULTS
  CA/CPR precipitated anxiety-like behavior and increased microglial activation and neuronal damage within the hippocampus relative to sham surgery. Prior exposure to stress exacerbated these measures among CA/CPR mice, but had no significant effect on sham-operated mice. Treatment with minocycline reduced both neuronal damage and anxiety-like behavior among CA/CPR animals. Anxiety-like behavior was significantly correlated with measures of microglial activation but not neuronal damage.
  
  
  CONCLUSIONS
  A history of stress exposure increases the pathophysiological response to ischemia and anxiety-like behavior, whereas inhibiting microglial activation reduces neuronal damage and mitigates the development of anxiety-like behavior after CA/CPR. Thus, modulating inflammatory signaling after cerebral ischemia may be beneficial in protecting the brain and preventing the development of affective disorders.
authors.affiliation: Department of Psychology, The Ohio State University, Columbus, Ohio 30322, USA.
authors.forename: Gretchen N
authors.initials: GN
authors.lastname: Neigh
authors.forename: Kate
authors.initials: K
authors.lastname: Karelina
authors.forename: Erica R
authors.initials: ER
authors.lastname: Glasper
authors.forename: Stephanie L K
authors.initials: SL
authors.lastname: Bowers
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Popovich
authors.forename: A Courtney
authors.initials: AC
authors.lastname: DeVries
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects; D006323:Heart Arrest / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology
chemical_list: D008911:Minocycline