Strategies and experimental models for evaluating anesthetics: effects on the developing nervous system

Area of Science:

• Neuroscience
• Developmental Biology
• Pharmacology

Background:

• Pediatric surgery advances increase anesthesia duration and complexity.
• Anesthetic drugs are known to cause dose-dependent apoptosis in the developing rat brain.
• Nonhuman primates serve as a relevant model for assessing anesthetic neurotoxicity due to physiological similarities to humans.

Purpose of the Study:

• To review anesthetic-induced neuronal cell death during development.
• To describe the application of pharmacogenomic and systems biology approaches for understanding anesthetic neurotoxicity.
• To discuss protection strategies against anesthetic-induced neuronal cell death in pediatric patients.

Main Methods:

• Review of preclinical experimental data, with a focus on ketamine.
• Utilizing nonhuman primate models to assess neurotoxic effects of anesthetics.
• Application of pharmacogenomic and systems biology approaches to study developmental neurotoxicity.

Main Results:

• Anesthetic drugs can induce widespread, dose-dependent apoptosis in the developing brain.
• The window of vulnerability is during rapid synaptogenesis (brain growth spurt period).
• N-methyl-d-aspartate antagonist drugs, as a class, warrant concern regarding neurodegeneration.

Conclusions:

• Further research is needed to address anesthetic-induced brain cell loss, class effects, drug interactions, and human vulnerability periods.
• Pharmacogenomic and systems biology approaches offer valuable tools for understanding anesthetic neurotoxicity.
• Minimizing risks requires a thorough understanding of anesthetic effects on the developing brain.