AUTHOR=Meng Bo , Li Xiaoyu , Lu Bo , Liu Rongjun , Yuan Hui , Zhai Xiaojie , Qin Jinling , Chen Zhang , Zheng Jinwei , Chen Junping 

TITLE=The Investigation of Hippocampus-Dependent Cognitive Decline Induced by Anesthesia/Surgery in Mice Through Integrated Behavioral Z-Scoring

JOURNAL=Frontiers in Behavioral Neuroscience

VOLUME=13

YEAR=2020

URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2019.00282

DOI=10.3389/fnbeh.2019.00282

ISSN=1662-5153

ABSTRACT=<sec><title>Objective</title><p>Patients undergoing major surgeries may experience certain cognitive decline, which is known as postoperative delirium (POD) or postoperative cognitive dysfunction (POCD). We employed integrated behavioral <italic>Z-</italic>scoring introduced by <xref ref-type="bibr" rid="B10">Guilloux et al. (2011)</xref> to investigate the effects of fracture fixation under anesthesia on hippocampus-dependent memory in mice.</p></sec><sec><title>Methods</title><p>ICR mice (12–14 months) underwent stabilized tibial fracture operation under sevoflurane anesthesia. They were subjected to a battery of successive hippocampus-dependent tests following surgery, including open field test (OF), novel object recognition (NOR), fear conditioning test (FC), and Morris water maze (MWM). The integrated behavioral <italic>Z-</italic>scoring was applied to assess the hippocampus-dependent memory after anesthesia/surgery, and the association between the integrated behavioral <italic>Z</italic>-scores and hippocampal pro-inflammatory cytokines was explored.</p></sec><sec><title>Results</title><p>Mice after anesthesia/surgery were found to have impaired hippocampus-dependent memory in NOR, FC, and MWM but with different degrees in these aspects as represented by <italic>P-</italic>value and effect size. The integrated memory <italic>Z</italic>-scores based on principal parameters of the above three tests can reduced the variability and increase the comprehensiveness of behavioral results. However, we found no statistic associations between hippocampal pro-inflammatory cytokines and the integrated <italic>Z</italic>-scores, as the elevated cytokines quickly return to normal on postoperative day 3 and/or day 7.</p></sec><sec><title>Conclusion</title><p>The integrated <italic>Z</italic>-score methodology could facilitate the interpretation of the anesthesia/surgery induced cognitive decline in mice and robustly quantify the behavioral phenotyping of hippocampus-dependent memory.</p></sec>