Neuroinflammation Induced by Surgery Does Not Impair the Reference Memory of Young Adult Mice
Neuroinflammation Induced by Surgery Does Not Impair the Reference Memory of Young Adult Mice
Yanhua Zhao,1 Lili Huang,1 Huan Xu,2 Guangxi Wu,1 Mengyi Zhu,3 Jie Tian,1 Hao Wang,4 Xiangrui Wang,1 Weifeng Yu,1 Liqun Yang,1 and Diansan Su1
1Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
2Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
3Department of Anesthesiology, Shanghai Tenth People’s Hospital, Shanghai, China
4Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai, China
Received 21 June 2016; Revised 13 September 2016; Accepted 21 September 2016
Academic Editor: Giuseppe Valacchi
Copyright © 2016 Yanhua Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Postoperative cognitive dysfunction (POCD) increases morbidity and mortality after surgery. But the underlying mechanism is not clear yet. While age is now accepted as the top one risk factor for POCD, results from studies investigating postoperative cognitive functions in adults have been controversial, and data about the very young adult individuals are lacking. The present study investigated the spatial reference memory, IL-1β, IL-6, and microglia activation changes in the hippocampus in 2-month-old mice after anesthesia and surgery. We found that hippocampal IL-1β and IL-6 increased at 6 hours after surgery. Microglia were profoundly activated in the hippocampus 6 to 24 hours after surgery. However, no significant behavior changes were found in these mice. These results indicate that although anesthesia and surgery led to neuroinflammation, the latter was insufficient to impair the spatial reference memory of young adult mice.
1. Introduction
Postoperative cognitive dysfunction (POCD) is the deterioration of cognitive function, especially learning and memory, which may last for days, months, or even years [1–3]. POCD occurs after cardiac and noncardiac surgeries and increases first-year morbidity and mortality after surgery [4–6]. However, the mechanism of POCD is unclear yet.
There is no doubt that aged individuals are more likely to develop POCD [7–9]. However, for the adult subjects, there is no clear conclusion. Maze’s group demonstrated that learning and memory were impaired after anesthesia and surgery in 3-4-month-old mice. Rosczyk et al. [10] demonstrated that there were no signs of neuroinflammation or cognition impairment after surgery in adult mice (4–6-month-old). Similarly, Wuri et al. [11] observed no learning or memory changes after partial hepatectomy in adult mice (4-month-old).
According to the work of Finlay and Darlington [12], mice after two months are considered adult. Accordingly, 3–6-month-old mice and 2-month-old mice are biologically equivalent to 30–40-year-old human and college freshmen, respectively [13]. While Maze’s group investigated the learning and memory after anesthesia and surgery in 3-4-month-old mice, no data in younger adult mice, that is, 2-month-old, are available. Unfortunately, this is an age at which particular diseases will arise and may need surgeries, such as appendicitis, osteosarcoma, and leukemia. In the present study, we investigated whether the spatial reference memory of 2-month-old mice will be affected after anesthesia and surgery.
2. Methods
This study was approved by the Animal Care and Use Committee of Shanghai Jiao Tong University, School of Medicine. All animal procedures were performed in accordance with the National Institutes of Health (NIH) animal care guidelines.
2.1. Animals and Experimental Grouping
Two-month-old male C57BL/6J mice were provided by the Animal Research Center of Shanghai Jiaotong University, School of Medicine. The animals were housed in standard cages under controlled laboratory conditions (temperature of °C, 12-hour light/12-hour dark cycle) with free access to regular rodent pellets and water. All mice were allowed to adapt to their new environment for 7 days before beginning the experiments.
Mice were randomly divided into three groups: naïve group, anesthesia group, and surgery group. Splenectomy [14] was performed with neuroleptic anesthesia (intraperitoneal injection of 200 μg/kg fentanyl and 10 mg/kg droperidol, as reported previously [15, 16]) in the surgery group. For the splenectomy, a small incision was made in the left upper abdominal quadrant, and the spleen was mobilized, isolated, and removed. The wound was infiltrated with 0.25% bupivacaine and closed by suture. A single dose of butorphanol (0.4 mg/kg, s.c.) was administered for postoperative analgesia at the end of surgery. An identical neuroleptic anesthesia regimen was administered to the mice in the anesthesia group. No interventions were condu (...truncated)