Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell models

Area of Science:

• Neuroscience
• Developmental Neurotoxicity
• Anesthesiology

Background:

• General anesthetics (GA), including desflurane, raise safety concerns due to potential neurodevelopmental effects.
• Neural stem cells (NSCs) are a valuable in vitro model for assessing anesthetic-induced neurotoxicity.
• Early-life exposure to anesthetics may cause neural cell death and behavioral changes.

Purpose of the Study:

• To investigate the temporal effects of desflurane exposure on neural stem cell health, proliferation, differentiation, and viability.
• To evaluate desflurane-induced developmental neurotoxicity using a monkey NSC model.

Main Methods:

• Harvested NSCs from gestational day 80 monkey hippocampus.
• Exposed NSCs to clinically relevant desflurane concentrations (5.7%) for short-term (3h) and prolonged (24h) periods.
• Assessed NSC viability (LDH release), proliferation (Cell Cycle Assay), differentiation, and expression of neural markers (PSA-NCAM) and cytokines.

Main Results:

• Desflurane exposure did not significantly alter NSC viability or proliferation at short or prolonged durations.
• Prolonged (24h) desflurane exposure significantly increased LDH release in differentiated neural cells.
• Desflurane exposure elevated pro-inflammatory cytokines and significantly reduced PSA-NCAM-positive differentiated neurons.

Conclusions:

• Clinically relevant desflurane concentrations do not induce NSC damage but impair differentiated neurons after prolonged exposure.
• Desflurane-induced neurotoxicity is linked to the loss of differentiated neurons, potentially mediated by changes in PSA-NCAM.
• Findings aid in understanding desflurane's effects on the developing brain and optimizing pediatric anesthetic use.