Objective: Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood; however, the underlying mechanism has not been established. Methods: SD rats were exposed to propofol on postnatal day 7 (PND-7). Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus (DG). The expression of p-Akt and p27 were measured by western blotting. The Morris water maze, novel object recognition test, and object location test were used to evaluate neurocognitive function 2-month-old rats. Results: Phosphorylation of Akt was inhibited, while p27 expression was enhanced after neonatal exposure to propofol. Propofol also inhibited proliferation of neural stem cells (NSCs) and decreased differentiation to neurons and astroglia. Moreover, the neurocognitive function in 2-month-old rats was weakened. Of significance, intra-hippocampal injection of the Akt activator, SC79, attenuated the inhibition of p-AKT and increase of p27 expression. SC79 also rescued the propofol-induced inhibition of NSC proliferation and differentiation. The propofol-induced neurocognition deficit was also partially reversed by SC79. Conclusion Taken together, these results suggest that neurogenesis is hindered by neonatal propofol exposure. Specifically, neonatal propofol exposure was shown to suppress the proliferation and differentiation of NSCs by inhibiting Akt/p27 signaling pathway.
Animals ; Cell Proliferation ; Hippocampus/metabolism* ; Neural Stem Cells ; Propofol/toxicity* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

The trans-sphenoidal resection of a recurred pituitary tumor was performed in a 42 years old man under general anesthesia with propofol and remifentanil. Neither massive bleeding nor hypotension was observed intraoperatively, but bradycardia was sustained over five hours. The patient did not suffer from hypertriglyceridemia and there was no evidence of drug toxicity or vigorous intervention during the surgery, however hyperamylasemia was observed one day after the surgery. It is presumed that vagal stimulation by propofol and remifentanil infusion might induce bradycardia and abnormal pancreatic enzyme secretion consequently.
Anesthesia, General ; Bradycardia ; Drug Toxicity ; Hemorrhage ; Humans ; Hyperamylasemia ; Hypertriglyceridemia ; Hypotension ; Piperidines ; Pituitary Neoplasms ; Propofol