Application of Nonhuman Primate Models in the Studies of Pediatric Anesthesia Neurotoxicity

Abstract

Numerous animal models have been used to study developmental neurotoxicity associated with short-term or prolonged exposure of common general anesthetics at clinically relevant concentrations. Pediatric anesthesia models using the nonhuman primate (NHP) may more accurately reflect the human condition because of their phylogenetic similarity to humans with regard to reproduction, development, neuroanatomy, and cognition. Although they are not as widely used as other animal models, the contribution of NHP models in the study of anesthetic-induced developmental neurotoxicity has been essential. In this review, we discuss how neonatal NHP animals have been used for modeling pediatric anesthetic exposure; how NHPs have addressed key data gaps and application of the NHP model for the studies of general anesthetic-induced developmental neurotoxicity. The appropriate application and evaluation of the NHP model in the study of general anesthetic-induced developmental neurotoxicity have played a key role in enhancing the understanding and awareness of the potential neurotoxicity associated with pediatric general anesthetics.

A Molecular Toolbox of Positron Emission Tomography Tracers for General Anesthesia Mechanism Research

“…As it is ethically unacceptable to conduct prospective clinical trials on the potential neurotoxicity of drugs in humans, the neurotoxic effects of compounds are usually tested in animals . There is disagreement regarding the clinical relevance of animal data, which is influenced by several factors that cannot be directly extrapolated to humans . First, most animal models lack surgical stimulation compared to clinical anesthesia.…”

“…317,324 [ 18 F]61 has been used for non-invasive monitoring of endogenous neural stem cell proliferation in normal and ischemic adult rat brains in vivo. 317,325 18 F-Labeled N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([ 18 F]FEPPA, [ 18 F]62; RCY = 34 ± 2% (n = 17), RCP > 99%, A m = 198 ± 125 GBq/μmol), 326 a specific translocation protein (TSPO) ligand, 22 has been used as a marker of microglial activation as a surrogate marker of neural injury. 222,308,312−314 Their physicochemical properties are described in Table 14.…”

“…290 There is disagreement regarding the clinical relevance of animal data, which is influenced by several factors that cannot be directly extrapolated to humans. 22 First, most animal models lack surgical stimulation compared to clinical anesthesia. Second, the methods of anesthesia administration are different, and animals cannot be monitored for hemodynamic or respiratory changes or humoral or inflammatory responses.…”

“…Positron emission tomography (PET) is a powerful imaging technique that enables the specific and sensitive assessment of biochemical and physiological changes in whole-body living organisms with pmol–nmol sensitivity. − As a whole-brain-penetrating imaging technique in the clinic, PET can visualize radiolabeled anesthetics or radiotracers interacting with anesthesia-related targets within or on cells. The combination of PET imaging and brain neurophysiology has brought innovation to the study of the mechanism of general anesthesia, − as it allows for a more comprehensive understanding of the biochemical and physiological processes involved. − …”

Nonhuman Primates and Developmental Anesthesia Neurotoxicity Research: Pitfalls of Surrogate Models and Déformation Professionnelle

“…In this issue of the Journal, Wang et al 1 provide us with a comprehensive review on the use of NHP to investigate the effects of general anesthesia on the developing brain. The authors are from the National Center for Toxicological Research (NCTR) and have a broad portfolio of investigations and reports on the toxicology of substances and drugs regulated by the US Food and Drug Administration (FDA).…”