Intranasal Insulin Prevents Anesthesia-Induced Cognitive Impairment and Chronic Neurobehavioral Changes

Yanxing Chen,Cheng-Xin Gong,Chun-Ling Dai,Zhe Wu,Baorong Zhang,Khalid Iqbal,Fei Liu

doi:10.3389/fnagi.2017.00136

Abstract

General anesthesia increases the risk for cognitive impairment post operation, especially in the elderly and vulnerable individuals. Recent animal studies on the impact of anesthesia on postoperative cognitive impairment have provided some valuable insights, but much remains to be understood. Here, by using mice of various ages and conditions, we found that anesthesia with propofol and sevoflurane caused significant deficits in spatial learning and memory, as tested using Morris Water Maze (MWM) 2–6 days after anesthesia exposure, in aged (17–18 months old) wild-type (WT) mice and in adult (7–8 months old) 3xTg-AD mice (a triple transgenic mouse model of Alzheimer’s disease (AD)), but not in adult WT mice. Anesthesia resulted in long-term neurobehavioral changes in the fear conditioning task carried out 65 days after exposure to anesthesia in 3xTg-AD mice. Importantly, daily intranasal administration of insulin (1.75 U/mouse/day) for only 3 days prior to anesthesia completely prevented the anesthesia-induced deficits in spatial learning and memory and the long-term neurobehavioral changes tested 65 days after exposure to anesthesia in 3xTg-AD mice. These results indicate that aging and AD-like brain pathology increase the vulnerability to cognitive impairment after anesthesia and that intranasal treatment with insulin can prevent anesthesia-induced cognitive impairment.

Highlights

The world population is growing old with the increase in life expectancy
We found that the adult mice showed no impairment in spatial reference learning post anesthesia, as indicated by the indistinguishable learning curves during training trials between the anesthesia-treated and control-treated mice (Figure 1A)
Probe trial performed 24 h after the last training session showed no significant differences in the latency to the former platform location (Figure 1B), the number of platform location crossings (Figure 1C), the percentage of time spent in the target quadrant (Figure 1D), the percentage of distance the mice swam in the target quadrant (Figure 1E) or the swim speed (Figure 1F)

Summary

Introduction

The world population is growing old with the increase in life expectancy. As a result, the number of aged individuals undergoing surgical procedures is increasing. The elderly patients are known to be at an increased risk of postoperative cognitive dysfunction (POCD; Hudson and Hemmings, 2011). Anesthesia may increase the risk for cognitive impairment and Alzheimer’s disease (AD), especially in the elderly (Seitz et al, 2011; Chen P.-L. et al, 2014; Patel et al, 2016). Population-based studies suggest that the elderly and other vulnerable individuals who are already cognitively impaired before surgery may be at Insulin Prevents Anesthesia-Induced Neurobehavioral Impairment increased risk of dementia (Chen C.-W. et al, 2014; Chen P.-L. et al, 2014; Patel et al, 2016; Sprung et al, 2016)

Methods

Results

Conclusion