Abstract
Postoperative cognitive dysfunction (POCD) is a significant clinical issue. Aging is a risk factor for POCD. It is known that not every patient develops POCD. This situation shall be similar in animals. Determination of POCD is individual-based in humans but group-based in animal studies. This difference prevents effective evaluation of biomarkers and interventions for POCD in preclinical studies. The objective of this study was to determine whether individual animal could be assessed for POCD by a system similar to that for patients. Seven-week old CD1 and 18-month old C57BL/6 male mice were subjected to right carotid arterial exposure under isoflurane anesthesia. Mice were evaluated by Barnes maze and fear conditioning either post-surgery alone or both prior to surgery and post-surgery. Surgery increased the time to identify the target box in Barnes maze when tested one day or 8 days after the training sessions and reduced freezing behavior in fear conditioning test. This phenomenon occurred in 7-week old animals with and without evaluation before the surgery and in 18-month old mice evaluated before and after surgery. Based on the method and criteria used for a human whose cognition was evaluated before and after surgery to assess individual decline of cognition, 7 in 21 mice in the surgical group and 1 in 21 mice in control group of 7-week old mice had cognitive dysfunction. Among 18-month old mice, 13 in 21 mice in the surgical group and 2 in 20 mice in the control group had cognitive dysfunction. The incidence of cognitive dysfunction in mice with surgery was higher than that in control mice no matter whether young adult (P = 0.045) or old mice (P < 0.001) were considered. These results indicate that surgery induces POCD in mice. Individual animal-based assessment can be used to identify animals with POCD.
Highlights
Postoperative cognitive dysfunction (POCD) is a significant clinical issue that is associated with increased mortality and morbidity [1,2,3]
The time for young adult mice to identify the target box was decreased with training no matter whether the mice had surgery or not
Consistent with previous studies [4, 7], group-based assessment showed that surgery induced learning and memory impairment because mice in the surgical group took longer than control mice to find the target box one day and eight days after the training sessions in the Barnes maze and had less freezing behavior than control mice in the fear conditioning test
Summary
Postoperative cognitive dysfunction (POCD) is a significant clinical issue that is associated with increased mortality and morbidity [1,2,3]. Most of the previous animal studies have tested animals only once after surgery to study POCD [48] This method of evaluation is obviously different from that used in patients and will not identify an individual animal that develops POCD, which may prevent effective. Similar to clinical situation [1], each mouse was tested by Barnes maze and fear conditioning (7-week old mice) or by Barnes maze, fear conditioning, novel object recognition and open field tests (18-month old mice). These behavior tests were performed between 10 am to 4 pm. After the completion of all behavioral tests, mice were euthanized by deep isoflurane anesthesia
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