Cardiac arrest with cardiopulmonary resuscitation reduces dendritic spine density in CA1 pyramidal cells and selectively alters acquisition of spatial memory.

Abstract

The hippocampus is highly sensitive to ischemia and is one of the most extensively damaged regions of brain during cardiac arrest. Damage to hippocampus can subsequently lead to learning and memory deficits. The current study used the Morris water maze to characterize spatial learning and memory deficits elicited by 8 min of cardiac arrest with cardiopulmonary resuscitation (CA/CPR) in mice, which is associated with a 25-50% decrease in CA1 neurons. Mice were trained to navigate the water maze prior to CA/CPR or sham surgery (SHAM). They were retested in the water maze on days 7 and 8 postsurgery; both CA/CPR and SHAM groups were able to perform the task at presurgical levels. However, when the hidden platform was moved to a new location, the SHAM mice were able to adapt more quickly to the change and swam a shorter distance in search of the platform than did CA/CPR mice. Thus, CA/CPR did not affect the ability of mice to retain a previously learned platform location, but it did affect their ability to learn a new platform location. This behavioural impairment was correlated with dendritic spine density in the CA1 region of the hippocampus. Data presented here suggest that morphological changes, such as spine density, that occur in neurons that survive CA/CPR may be associated with cognitive impairments.