Anesthetic-induced neurodevelopmental changes with region-specific responses to propofol in forebrain organoids

Summary Propofol, a common anesthetic, has unclear effects on fetal brain development. While previous studies in animal models and 2D culture systems have reported neurotoxic effects, few have addressed the region-specific vulnerability of the developing human brain. This study investigated the distinct effects of propofol on human dorsal (hCS) and ventral (hSS) forebrain organoids, uncovering region-specific differences in neuronal differentiation and maturation. Detailed electrophysiological analysis revealed that propofol enhanced neuronal activity—increased action potential frequency and amplitude—in hCS organoids. Transcriptomic analysis further indicated a metabolic shift away from hypoxic stress toward efficient aerobic pathways. These findings provide a deeper understanding of how anesthesia affects brain development, particularly in early stages, and highlight the importance of considering regional differences and long-term effects in future research.