Abstract
Propofol is a general anesthetic widely used in surgical procedures, including those in pregnant women. Preclinical studies suggest that propofol may cause neuronal injury to the offspring of primates if it is administered during pregnancy. However, it is unknown whether those neuronal changes would lead to long-term behavioral deficits in the offspring. In this study, propofol (0.4 mg/kg/min, IV, 2 h), saline, or intralipid solution was administered to pregnant rats on gestational day 18. We detected increased levels of cleaved caspase-3 in fetal brain at 6 h after propofol exposure. The neuronal density of the hippocampus of offspring was reduced significantly on postnatal day 10 (P10) and P28. Synaptophysin levels were also significantly reduced on P28. Furthermore, exploratory and learning behaviors of offspring rats (started at P28) were assessed in open-field trial and eight-arm radial maze. The offspring from propofol-treated dams showed significantly less exploratory activity in the open-field test and less spatial learning in the eight-arm radial maze. Thus, this study suggested that propofol exposure during pregnancy in rat increased cleaved caspsase-3 levels in fetal brain, deletion of neurons, reduced synaptophysin levels in the hippocampal region, and persistent learning deficits in the offspring.
Highlights
General anesthetics have been used safely for surgery in adults for decades [1], their use in pregnancy is becoming a more concerning issue due to their potential effects on the immature or developing brain [2,3,4]
PvCO2, PvO2, HCO3−, and pH did not differ significantly from baseline (Table 1). Taking these measures and maintaining the vital signs reduced the possibility that propofol-induced neurodegeneration in the fetal brains was caused by physiologic side effects
We intravenously infused propofol into pregnant (G18) rats to study the neurotoxic effects of propofol in the offspring brain. We found that this manipulation caused: (A) a significant increase in the levels of cleaved caspase-3 in fetal brain 6 h after propofol exposure. (B) A
Summary
General anesthetics have been used safely for surgery in adults for decades [1], their use in pregnancy is becoming a more concerning issue due to their potential effects on the immature or developing brain [2,3,4]. Anesthetic administration during pregnancy would lead to a significant amount of general anesthetic exposure to the fetus and its long-term effects on human fetal brain development remain unclear. Especially in vivo system, are needed in this field to verify the link between general anesthetics early exposure to immature brain and the possible neurotoxicity. The effects of the inhalational general anesthetic on fetal brain development have been extensively studied in animal models by multiple laboratories.
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