Propofol and remifentanil at moderate and high concentrations affect proliferation and differentiation of neural stem/progenitor cells

Propofol and remifentanil alter intracellular Ca(2+) concentration ([Ca(2+)](i)) in neural stem/progenitor cells by activating γ-aminobutyric acid type A receptors and by reducing testosterone levels. However, whether this process affects neural stem/progenitor cell proliferation and differentiation remains unknown. In the present study, we applied propofol and remifentanil, alone or in combination, at low, moderate or high concentrations (1, 2–2.5 and 4–5 times the clinically effective blood drug concentration), to neural stem/progenitor cells from the hippocampi of newborn rat pups. Low concentrations of propofol, remifentanil or both had no noticeable effect on cell proliferation or differentiation; however, moderate and high concentrations of propofol and/or remifentanil markedly suppressed neural stem/progenitor cell proliferation and differentiation, and induced a decrease in [Ca(2+)](i) during the initial stage of neural stem/progenitor cell differentiation. We therefore propose that propofol and remifentanil interfere with the proliferation and differentiation of neural stem/progenitor cells by altering [Ca(2+)](i). Our findings suggest that propofol and/or remifentanil should be used with caution in pediatric anesthesia.