PMID- 37208914
OWN - NLM
STAT- MEDLINE
DCOM- 20230720
LR  - 20240117
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 248
IP  - 7
DP  - 2023 Apr
TI  - Development of a primate model to evaluate the effects of ketamine and surgical 
      stress on the neonatal brain.
PG  - 624-632
LID - 10.1177/15353702231168144 [doi]
AB  - With advances in pediatric and obstetric surgery, pediatric patients are subject 
      to complex procedures under general anesthesia. The effects of anesthetic 
      exposure on the developing brain may be confounded by several factors including 
      pre-existing disorders and surgery-induced stress. Ketamine, a noncompetitive 
      N-methyl-d-aspartate (NMDA) receptor antagonist, is routinely used as a pediatric 
      general anesthetic. However, controversy remains about whether ketamine exposure 
      may be neuroprotective or induce neuronal degeneration in the developing brain. 
      Here, we report the effects of ketamine exposure on the neonatal nonhuman primate 
      brain under surgical stress. Eight neonatal rhesus monkeys (postnatal days 5-7) 
      were randomly assigned to each of two groups: Group A (n = 4) received 2 mg/kg 
      ketamine via intravenous bolus prior to surgery and a 0.5 mg/kg/h ketamine 
      infusion during surgery in the presence of a standardized pediatric anesthetic 
      regimen; Group B (n = 4) received volumes of normal saline equivalent to those of 
      ketamine given to Group A animals prior to and during surgery, also in the 
      presence of a standardized pediatric anesthetic regimen. Under anesthesia, the 
      surgery consisted of a thoracotomy followed by closing the pleural space and 
      tissue in layers using standard surgical techniques. Vital signs were monitored 
      to be within normal ranges throughout anesthesia. Elevated levels of cytokines 
      interleukin (IL)-8, IL-15, monocyte chemoattractant protein-1 (MCP-1), and 
      macrophage inflammatory protein (MIP)-1beta at 6 and 24 h after surgery were 
      detected in ketamine-exposed animals. Fluoro-Jade C staining revealed 
      significantly higher neuronal degeneration in the frontal cortex of 
      ketamine-exposed animals, compared with control animals. Intravenous ketamine 
      administration prior to and throughout surgery in a clinically relevant neonatal 
      primate model appears to elevate cytokine levels and increase neuronal 
      degeneration. Consistent with previous data on the effects of ketamine on the 
      developing brain, the results from the current randomized controlled study in 
      neonatal monkeys undergoing simulated surgery show that ketamine does not provide 
      neuroprotective or anti-inflammatory effects.
FAU - Wang, Cheng
AU  - Wang C
AUID- ORCID: 0000-0002-8315-6232
AD  - Division of Neurotoxicology, National Center for Toxicological Research, Food and 
      Drug Administration (FDA), Jefferson, AR 72079, USA.
FAU - Bhutta, Adnan
AU  - Bhutta A
AUID- ORCID: 0000-0003-3362-5835
AD  - University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
AD  - Riley Children's Hospital, Indiana University School of Medicine, Indianapolis, 
      IN 46202, USA.
FAU - Zhang, Xuan
AU  - Zhang X
AD  - Division of Neurotoxicology, National Center for Toxicological Research, Food and 
      Drug Administration (FDA), Jefferson, AR 72079, USA.
FAU - Liu, Fang
AU  - Liu F
AUID- ORCID: 0000-0002-4568-3859
AD  - Division of Neurotoxicology, National Center for Toxicological Research, Food and 
      Drug Administration (FDA), Jefferson, AR 72079, USA.
FAU - Liu, Shuliang
AU  - Liu S
AD  - Division of Neurotoxicology, National Center for Toxicological Research, Food and 
      Drug Administration (FDA), Jefferson, AR 72079, USA.
FAU - Latham, Leah E
AU  - Latham LE
AD  - Division of Neurotoxicology, National Center for Toxicological Research, Food and 
      Drug Administration (FDA), Jefferson, AR 72079, USA.
FAU - Talpos, John C
AU  - Talpos JC
AD  - Division of Neurotoxicology, National Center for Toxicological Research, Food and 
      Drug Administration (FDA), Jefferson, AR 72079, USA.
FAU - Patterson, Tucker A
AU  - Patterson TA
AD  - Office of Research, National Center for Toxicological Research, Food and Drug 
      Administration (FDA), Jefferson, AR 72079, USA.
FAU - Slikker, William Jr
AU  - Slikker W Jr
AUID- ORCID: 0000-0002-9616-9462
AD  - Retired.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial, Veterinary
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20230519
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Anesthetics)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - *Anesthetics/pharmacology
MH  - Animals, Newborn
MH  - Brain/metabolism
MH  - *Ketamine/pharmacology
MH  - Primates
PMC - PMC10350805
OTO - NOTNLM
OT  - Brain
OT  - anesthesia
OT  - developmental
OT  - neuroscience
OT  - neurotoxicology
OT  - surgery
COIS- The author(s) declared no potential conflicts of interest with respect to the 
      research, authorship, and/or publication of this article.
EDAT- 2023/05/20 09:42
MHDA- 2023/07/17 06:41
PMCR- 2023/11/19
CRDT- 2023/05/20 03:40
PHST- 2023/07/17 06:41 [medline]
PHST- 2023/05/20 09:42 [pubmed]
PHST- 2023/05/20 03:40 [entrez]
PHST- 2023/11/19 00:00 [pmc-release]
AID - 10.1177_15353702231168144 [pii]
AID - 10.1177/15353702231168144 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2023 Apr;248(7):624-632. doi: 10.1177/15353702231168144. 
      Epub 2023 May 19.