Rats Exposed to Isoflurane In Utero  during Early Gestation Are Behaviorally Abnormal as Adults

Abstract

Background: Preclinical evidence suggests that commonly used anesthetic agents induce long-lasting neurobehavioral changes when administered early in life, but there has been virtually no attention to the neurodevelopmental consequences for the fetus of maternal anesthesia. This study tested the hypothesis that fetal rats exposed to isoflurane during maternal anesthesia on gestational day 14, which corresponds to the second trimester in humans, would be behaviorally abnormal as adults. Methods: Timed, pregnant rats were randomly assigned on gestational day 14 to receive 1.4% isoflurane in 100% oxygen (n ϭ 3) or 100% oxygen (n ϭ 2) for 4 h. Beginning at 8 weeks of age, male offspring (N ϭ 12-14 in control and anesthesia groups, respectively) were evaluated for spontaneous locomotor activity, hippocampal-dependent learning and memory (i.e., spontaneous alternations, novel object recognition, and radial arm maze), and anxiety (elevated plus maze).

Nonobstetric anesthesia during pregnancy

“…This finding comes from mice, thereby illustrating that a neurotoxic potential of anesthetics seems to be given in various species. When administered to rats at a gestational age corresponding to the second human trimester isoflurane caused behavioral abnormalities, that is, an impaired acquisition of spatial working memory [19]. This finding was very interesting because it contradicted the results by Li and colleagues [20] who were unable to find an effect during a later gestational period.…”

“…However, there were several limitation to this study, including the study of only male animals. Moreover, Palanisamy et al [19] respirated their animal with 100% oxygen and high oxygen fractions are known to have a detrimental effect on neurodevelopment [21]. The results may have been different with lower oxygen concentrations although a high oxygen fraction may be chosen by many practitioners to ensure oxygenation of mother and baby.…”

Sedation and anaesthesia for non-obstetric surgery

“…In the last few years, warning have been raised secondary to animal studies showing an accelerated neuronal apoptosis associated with abnormal behaviour in immature rodents exposed to anaesthetic agents, such as propofol [41,42], sevoflurane [43] or isoflurane [44].…”

Propofol exposure during early gestation impairs learning and memory in rat offspring by inhibiting the acetylation of histone

“…Accumulating evidence indicates general anaesthetics exposure during pregnancy may cause neurotoxic effects and induce persistent cognitive dysfunction of offspring rats 1, 2, 3. Propofol is commonly used in pregnancy for non‐obstetric surgery.…”