PMID- 24780497
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20220331
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 68
DP  - 2014 Aug
TI  - Ketamine administered to pregnant rats in the second trimester causes 
      long-lasting behavioral disorders in offspring.
PG  - 145-55
LID - S0969-9961(14)00051-5 [pii]
LID - 10.1016/j.nbd.2014.02.009 [doi]
AB  - Commonly used anesthetic agents, e.g. ketamine, may be neurotoxic to the 
      developing brain but there has been little attention to the neurobehavioral 
      consequences for offspring when used for maternal anesthesia. We hypothesize that 
      treatment of pregnant rats with ketamine during the second trimester would affect 
      brain development of the offspring. Pregnant rats on gestational day 14, about 
      equal to midtrimester pregnancy in humans, received a sedative dose of ketamine 
      intravenously for 2h. Brain hippocampal morphology of their pups at postnatal 
      days 0 (P0) and P30 was examined by Nissl-staining and the characteristics of 
      dendrites were determined using the Golgi-Cox staining, while cell proliferation 
      in subventricular zone (SVZ) and dentate gyrus (DG) was labeled with 
      bromodeoxyuridine (BrdU). Their neurobehavioral functions were tested at P25-30 
      after which the NR1 and NR2 subunits of N-methyl-d-aspartate (NMDA) receptor, 
      brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 
      (PSD-95) in the hippocampus were analyzed by western blot. When pregnant rats 
      were exposed to ketamine, there was neuronal loss, pyramidal neuronal abnormality 
      and reduced cell proliferation in the hippocampus of offspring. These 
      morphological abnormalities were associated with depression- and anxiety-like 
      behaviors, and impaired memory up to young adult age. The treatment further 
      caused NR2A receptor subunit up-regulation and NR2B receptor subunit, BDNF and 
      PSD-95 down-regulation. These data suggest that maternal anesthesia with ketamine 
      during the fetal brain development period can cause fetal brain damage and 
      subsequent neurobehavioral abnormality, which is likely associated with the 
      imbalanced expression of NMDA receptor subunits.
CI  - Copyright (c) 2014. Published by Elsevier Inc.
FAU - Zhao, Tianyun
AU  - Zhao T
AD  - Department of Anesthesiology, Shenzhen Maternity and Child healthcare Hospital, 
      Southern Medical University, Shenzhen 518028, China.
FAU - Li, Yuantao
AU  - Li Y
AD  - Department of Anesthesiology, Shenzhen Maternity and Child healthcare Hospital, 
      Southern Medical University, Shenzhen 518028, China. Electronic address: 
      sylyt6788@sina.com.
FAU - Wei, Wei
AU  - Wei W
AD  - Department of Anesthesiology, Meizhou people's hospital, Meizhou, Guangdong 
      514031, China.
FAU - Savage, Sinead
AU  - Savage S
AD  - Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery & Cancer, 
      Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, 
      London, UK.
FAU - Zhou, Libing
AU  - Zhou L
AD  - Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, 
      Guangzhou, Guangdong 510632, China. Electronic address: tlibingzh@jnu.edu.cn.
FAU - Ma, Daqing
AU  - Ma D
AD  - Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery & Cancer, 
      Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, 
      London, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140426
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Analgesics)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Age Factors
MH  - Analgesics/*toxicity
MH  - Animals
MH  - Animals, Newborn
MH  - Body Temperature/drug effects
MH  - Cell Proliferation/drug effects
MH  - Disease Models, Animal
MH  - Exploratory Behavior/drug effects
MH  - Female
MH  - Food Preferences/drug effects
MH  - Gene Expression Regulation, Developmental/drug effects/physiology
MH  - Gestational Age
MH  - Hippocampus/drug effects/growth & development/pathology
MH  - Ketamine/*toxicity
MH  - Lateral Ventricles/drug effects/metabolism/pathology
MH  - Male
MH  - Maze Learning/drug effects
MH  - Mental Disorders/*etiology/pathology/physiopathology
MH  - Neurons/metabolism/pathology/ultrastructure
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*chemically induced/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - Brain development
OT  - Cognition
OT  - Depression
OT  - Ketamine
OT  - NMDA receptor
OT  - Pregnancy
EDAT- 2014/05/02 06:00
MHDA- 2015/05/12 06:00
CRDT- 2014/05/01 06:00
PHST- 2013/11/16 00:00 [received]
PHST- 2014/02/21 00:00 [revised]
PHST- 2014/02/25 00:00 [accepted]
PHST- 2014/05/01 06:00 [entrez]
PHST- 2014/05/02 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
AID - S0969-9961(14)00051-5 [pii]
AID - 10.1016/j.nbd.2014.02.009 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2014 Aug;68:145-55. doi: 10.1016/j.nbd.2014.02.009. Epub 2014 Apr 
      26.