Histopathological and behavioral characterization of a novel model of cardiac arrest and cardiopulmonary resuscitation in mice.
Cardiac arrest is associated with high mortality and poor neurological outcome. We characterized functional and histological outcome in a novel mouse model of cardiac arrest and cardiopulmonary resuscitation (CPR) in order to study neuroprotective mechanisms. Cardiac arrest was induced in male C57Bl/6 and 129SVEV mice by i.v. injection of KCl. After 10 min cardiac standstill, CPR was initiated by administration of epinephrine, ventilation with 100% oxygen and chest compressions. Twenty-four hours before and 3 or 7 days after CPR, mice were subjected to behavioral testing using a passive avoidance task, locomotor activity in an open field, and spontaneous alternation in a T-maze. Hippocampal and caudoputamen injury was quantified 3 or 7 days after CPR. At both time points, caudoputamen injury was worse in 129SVEV mice. Post-ischemic mice of both strains showed a reduced number of correct choices in the T-maze up to 7 days after CPR, and were temporarily impaired in learning the passive avoidance task with a retention deficit on day 3 but not on day 7. Locomotor activity showed strain differences with C57Bl/6 mice being more active, but little ischemia-related effects. A dissociation between functional and histological outcome was found emphasizing the importance of combining both outcome measures for evaluation of neuroprotective strategies.
Kofler
Julia
J
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Hattori
Kimihiko
K
Sawada
Masahiko
M
DeVries
A Courtney
AC
Martin
Lee J
LJ
Hurn
Patricia D
PD
Traystman
Richard J
RJ
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000473:pathology / Q000502:physiology; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology*; D017202:Myocardial Ischemia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D013045:Species Specificity