Visual recognition memory is impaired in rhesus monkeys repeatedly exposed to sevoflurane in infancy

Abstract

Background: Experimental studies in animals have shown that exposure to general anaesthesia in infancy can cause loss of cells in the central nervous system and long-term impairments in neurocognitive function. Some human epidemiological studies have shown increased risk of learning disability after repeated anaesthesia exposure in early childhood. Thus, we investigated in a highly translational rhesus monkey model, whether repeated exposure in infancy to the inhalation anaesthetic sevoflurane is associated with impaired visual recognition memory during the first two yr of life.

Methods: Rhesus monkeys of both sexes were exposed to sevoflurane inhalation anaesthesia on approximately postnatal day 7 and then again 14 and 28 days later, for four h each time. Visual recognition memory was tested using the visual paired comparison task, which measures memory by assessing preference for looking at a new image over a previously-viewed image. Monkeys were tested at 6-10 months of age, again at 12-18 months of age, and again at 24-30 months of age.

Results: No memory impairment was detected at 6-10 months old, but significant impairment (reduced time looking at the novel image) was observed at 12-18 and 24-30 months old.

Conclusions: Repeated exposure of infant rhesus monkeys to sevoflurane results in visual recognition memory impairment that emerges after the first yr of life. This is consistent with epidemiological studies that show increased risk of learning disability after repeated exposure to anaesthesia in infancy/early childhood. Moreover, these deficits may emerge at later developmental stages, even when memory performance is unaffected earlier in development.

Keywords: cognitive disorder; general anaesthesia; macaque, rhesus; neurotoxicity syndromes; sevoflurane.

Fig 1

Illustration of a single trial of the visual paired comparison task.

Fig 2

Neonatal sevoflurane exposure had a delayed impact on memory performance as measured by the VPC task. Performance was analysed separately at each of three age ranges, therefore the effects of sevoflurane exposure across the four delays (pink lines) vs controls (blue lines) are presented in the three panels: six-10 months, 12-18 months, and 24-30 months (see text). Anaesthesia exposed monkeys were unimpaired when tested at six-10 months (left panel). However they displayed a delay-dependent deficit at 12-18 months (centre panel). In contrast, at 24-30 months of age, monkeys that were exposed to sevoflurane three times in the first month of life showed a delay-independent impairment with respect to control subjects. Control subjects shown in blue; anaesthesia exposed subjects shown in pink. Error bars indicate the SEM.