Original Article
Effects of ifenprodil on isoflurane-induced impairment of learning and memory
Zhang Peng, Xu Fangxia, Cui Yin, Song Jia, Liu Huan, Gu Xiaoping
Published 2018-11-15
Cite as Int J Anesth Resus, 2018,39(11): 1038-1042. DOI: 10.3760/cma.j.issn.1673-4378.2018.11.009
Abstract
ObjectiveTo investigate the long-term effects of intracerebroventricular administration of ifenprodil, a N-methyl-D-aspartate receptor subunit 2B(NR2B) receptor antagonist, on isoflurane-induced impairment of learning and memory in mice.
MethodsEighty male C57BL/6 mice (8 weeks old) were randomly divided into five groups (n=16): mice in control group (group C) inhaled O2 for 6 h. Those in sham group (group S) inhaled O2 for 6 h after intracerebroventricular injection of 2 μl NS. Those in isoflurane group (group A) inhaled 1.3% isoflurane for 6 h after intracerebroventricular injection of 2 μl NS. Those in isoflurane + ifenprodil group (group AI) inhaled 1.3% isoflurane for 6 h after intracerebroventricular injection of 2 μg ifenprodil (in 2 μl). Those in Ifenprodil group (group I) inhaled O2 for 6 h after intracerebro-ventricular injection of 2 μg ifenprodil (in 2 μl). The learning and memory of the mice 3 d and 7 d after anesthesia was examined by new object recognition (NOR) and contextual fear conditioning test (FC). NR2B mRNA expression in the hippocampus was semi-quantified with quantitative real time polymerase chain reaction(q-PCR).
ResultsThree and seven days after anesthesia, mice in group A showed decreased discrimination index for novel vs. familiar objects, compared with the group S (P<0.05). Compared with group A, group AI exhibited an increased discrimination index (P<0.05). Three d and 7 d after anesthesia, the percentage of freezing time in group A in FC significantly decreased (P<0.05), compared with that of group S. Compared with group A, group AI showed an increased percentage of freezing time (P<0.05). The q-PCR data showed that immediately after anesthesia, NR2B mRNA levels in the hippocampus were elevated in group A, compared with the group S (P<0.05). However, 3 d and 7 d after anesthesia, NR2B mRNA levels in the hippocampus reduced in group A, compared with group S (P<0.05). Compared with the group A, group AI had higher levels of NR2B mRNA in the hippocampus (P<0.05). Immediately or 3 d and 7 d after anesthesia, compared with group S, group I had lower levels of NR2B mRNA in the hippocampus, but there was no statistical significance (P>0.05).
ConclusionsIntracerebroventricular administration of ifenprodil before anaesthesia can decrease isoflurane-induced impairment of learning and memory in mice probably by reducing NR2B expression in the hippocampus.
Key words:
Ifenprodil; Impairment of learning and memory; Ifenprodil; N-methyl-D-aspartate receptor subunit 2B receptor
Contributor Information
Zhang Peng
Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Jiangsu Province, Nanjing 210008, China
Xu Fangxia
Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Jiangsu Province, Nanjing 210008, China
Cui Yin
Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Jiangsu Province, Nanjing 210008, China
Song Jia
Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Jiangsu Province, Nanjing 210008, China
Liu Huan
Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Jiangsu Province, Nanjing 210008, China
Gu Xiaoping
Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Jiangsu Province, Nanjing 210008, China
