Abstract
BackgroundEvaluating beneficial effects of potential protective therapies following cardiac arrest in rodent models could be enhanced by exploring behavior and cognitive functions. The Morris Water Maze is a well-known cognitive paradigm to test spatial learning and memory.ResultsBehavioral testing with the Morris Water Maze in Sprague–Dawley rats (300 ± 25 g) resuscitated after 8 min of ventricular fibrillation cardiac arrest was carried out 5 and 12 weeks after cardiac arrest (CA) and compared to results of naïve rats (Control).At 5 weeks, within each group latency time to reach the hidden platform (reflecting spatial learning) decreased equally from day 1 to 4 (CA: 105.6 ± 8.2 vs. 8.9 ± 1.2 s, p < 0.001; Control: 75.5 ± 13.2 vs. 17.1 ± 4.5, p < 0.001) with no differences between groups (p = 0.138). In the probe trial 24 h after the last trial, time spent in the target sector (reflecting memory recall) within each group was significantly longer (CA: 25 ± 1.3; Control: 24.7 ± 2.5 s) than in each of the three other sectors (CA: 7.7 ± 0.7, 14.3 ± 2.5, 8.4 ± 0.8 and Control: 7.8 ± 1.2, 11.7 ± 1.5, 10.3 ± 1.6 s) but with no significantly differences between groups. Seven days later (reflecting memory retention), control group animals remained significantly longer in the target sector compared to every other sector, whereas the cardiac arrest group animals did not. Even 12 weeks after cardiac arrest, the single p values showed that the control animals displayed a trend to perform better than the resuscitated animals.ConclusionsMemory recall was impaired early after 8 min of ventricular fibrillation cardiac arrest and might be a more valuable tool for cognitive testing than learning recall after global ischemia due to cardiac arrest.
Highlights
Evaluating beneficial effects of potential protective therapies following cardiac arrest in rodent models could be enhanced by exploring behavior and cognitive functions
Our results showed no difference between the groups in learning performance, neither in the acquisition phase nor in memory recall during the probe trials on day 5 (Fig. 3a and b) One week later, all the rats including controls and cardiac arrest group did not spend a significantly longer period of time in the target sector (Fig. 3c)
This might be caused by the influence of increasing age of animals on learning and memory behavior as reported by Morris [14] and D’ Hooge [21] or might be explained by factors reported by Langdon et al [22] who suggest a spontaneous repopulation of cornu ammonis 1 region (CA1) cells weeks after the ischemic insult
Summary
Evaluating beneficial effects of potential protective therapies following cardiac arrest in rodent models could be enhanced by exploring behavior and cognitive functions. Animal models have helped to find new therapeutic strategies to reduce injuries from global ischemia and reperfusion following prolonged, untreated cardiac arrest [3,4,5,6]. We have recently established a rat ventricular fibrillation cardiac arrest model to investigate pathophysiologic mechanisms of cerebral ischemia and reperfusion. Compared to our well-established pig model [7,8,9,10,11], it proved more difficult to generate ventricular fibrillation cardiac arrest survivors with considerable and consistent neurological damage in rats than in pigs with conventional resuscitation therapies. To generate a target for new therapeutic strategies, it seemed necessary to develop more sophisticated outcome tools to detect subtle neurologic sequelae from cardiac arrest in these
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