PMID- 33981208
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210514
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 13
DP  - 2021
TI  - Surgery Performed Under Propofol Anesthesia Induces Cognitive Impairment and 
      Amyloid Pathology in ApoE4 Knock-In Mouse Model.
PG  - 658860
LID - 10.3389/fnagi.2021.658860 [doi]
LID - 658860
AB  - Background: Postoperative cognitive dysfunction (POCD) following anesthesia and 
      surgery is a common and severe complication, especially in elderly patients. A 
      pre-existing cognitive impairment may impart susceptibility to further cognitive 
      dysfunction; the mechanism remains unclear. We hypothesized that the specific 
      impacts of anesthesia and surgery on individuals with preclinical Alzheimer's 
      disease (AD) may render them more susceptible to an increase in the risk of 
      cognitive impairment. The aim of this study was to compare the cognitive 
      impairment between normal adult mice and those with preclinical AD after propofol 
      anesthesia and surgery. Methods: We performed abdominal surgery in cognitively 
      pre-symptomatic, 5-month-old male mice with sporadic AD (apolipoprotein E4 
      allele, ApoE4-KI) and age-matched (C57BL/6J) controls. Propofol anesthesia (170 
      mg/kg) was induced via retro-orbital injection over 2 h. Morris water maze (MWM) 
      and Y-maze tests were conducted 2 days before and 2, 4, and 7 days after surgery. 
      The mean escape latencies and spontaneous alternation percentages were the major 
      outcomes. Neuronal apoptosis in hippocampal sections was evaluated using the 
      terminal dUTP nick-end labeling (TUNEL) assay. Hippocampal amyloid beta (Abeta) 
      levels were assessed via quantitative immunohistochemistry (IHC). Results: The 
      control mice exhibited increased mean escape latencies of MWM at postoperative 2 
      and 4, but not at day 7; ApoE4-KI mice exhibited such increases at postoperative 
      days 2, 4 and 7. Significant differences between ApoE4-KI and control mice in 
      terms of the mean escape latencies were evident at days 2 and 7 (both P < 0.05). 
      However, performance on a non-hippocampal memory tasks (Y-maze test) did not 
      differ. More TUNEL-positive neurons were evident in the hippocampal CA3 region of 
      ApoE4-KI mice at postoperative days 2 and 4, but not at day 7 compared to the 
      control group (both P < 0.05). IHC revealed significantly elevated Abeta deposition 
      in the hippocampal CA3 region of ApoE4-KI mice at postoperative days 4 and 7 
      compared to control mice (both P < 0.05). Conclusions: Propofol anesthesia 
      followed by surgery induced persistent changes in cognition, and pathological 
      hippocampal changes in pre-symptomatic, but vulnerable AD mice. It would be 
      appropriate to explore whether preclinical AD patients are more vulnerable to 
      POCD development.
CI  - Copyright (c) 2021 Kim, Jung, Lee and Sohn.
FAU - Kim, Jong-Ho
AU  - Kim JH
AD  - Department of Anesthesiology and Pain Medicine, Chuncheon Sacred Heart Hospital, 
      Hallym University College of Medicine, Chuncheon, South Korea.
AD  - Institute of New Frontier Research, College of Medicine, Hallym University, 
      Chuncheon, South Korea.
FAU - Jung, Harry
AU  - Jung H
AD  - Institute of New Frontier Research, College of Medicine, Hallym University, 
      Chuncheon, South Korea.
FAU - Lee, Yeonkyeong
AU  - Lee Y
AD  - Institute of New Frontier Research, College of Medicine, Hallym University, 
      Chuncheon, South Korea.
FAU - Sohn, Jong-Hee
AU  - Sohn JH
AD  - Institute of New Frontier Research, College of Medicine, Hallym University, 
      Chuncheon, South Korea.
AD  - Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University 
      College of Medicine, Chuncheon, South Korea.
LA  - eng
PT  - Journal Article
DEP - 20210426
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC8107235
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - anesthesia
OT  - post operative cognitive dysfunction
OT  - propofol
OT  - surgery
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/05/14 06:00
MHDA- 2021/05/14 06:01
PMCR- 2021/01/01
CRDT- 2021/05/13 06:24
PHST- 2021/01/27 00:00 [received]
PHST- 2021/03/30 00:00 [accepted]
PHST- 2021/05/13 06:24 [entrez]
PHST- 2021/05/14 06:00 [pubmed]
PHST- 2021/05/14 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2021.658860 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2021 Apr 26;13:658860. doi: 10.3389/fnagi.2021.658860. 
      eCollection 2021.