Anxiety after cardiac arrest/cardiopulmonary resuscitation: exacerbated by stress and prevented by minocycline.
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.
Neigh
Gretchen N
GN
Department of Psychology, The Ohio State University, Columbus, Ohio 30322, USA.
Karelina
Kate
K
Glasper
Erica R
ER
Bowers
Stephanie L K
SL
Zhang
Ning
N
Popovich
Phillip G
PG
DeVries
A Courtney
AC
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
D008911:Minocycline