Multiple Anesthetic Exposure in Infant Monkeys Alters Emotional Reactivity to an Acute Stressor

Abstract

Background Retrospective studies in humans have shown a higher prevalence of learning disabilities in children that received multiple exposures to general anesthesia before the age of 4. Animal studies, primarily in rodents, have found that postnatal anesthetic exposure causes neurotoxicity and neurocognitive deficits in adulthood. We addressed the question of whether repeated postnatal anesthetic exposure was sufficient to cause long-term behavioral changes in a highly translationally relevant rhesus monkey model, allowing study of these variables against a background of protracted nervous system and behavioral development. Methods Rhesus monkeys of both sexes underwent either three 4-hour exposures to sevoflurane anesthesia (anesthesia group n=10) or brief maternal separations (control group n=10) on postnatal day 6-10 that were repeated 14 and 28 days later. Monkeys remained with their mothers in large social groups at all times except for overnight observation after each anesthetic/control procedure. At 6 months of age, each monkey was tested on the human intruder paradigm, a common test for emotional reactivity in nonhuman primates. Results The frequency of anxiety-related behaviors was significantly higher in monkeys that were exposed to anesthesia as neonates as compared to controls: anesthesia 11.04 ± 1.68, controls 4.79 ± 0.77, M ± SEM (mean ± standard error of the mean) across all stimulus conditions. Conclusion Increased emotional behavior in monkeys after anesthesia exposure in infancy may reflect long-term adverse effects of anesthesia.

Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques

“…However, we found that recognition memory at six months of age, as measured by the VPC task, was similar in ZIKV-infected RM infants and uninfected controls, indicating selective sparing of this function. Although performance on the VPC task in adults is impacted by hippocampal damage, a lack of memory deficit in infancy was also reported in animals with selective damage to the hippocampal formation (75) or exposure to anesthesia (45) that result in similar emotional changes (41, 76). Interestingly, RM infants with experimental selective hippocampal lesions evidenced a late-developing delay-dependent memory impairment as they reached adulthood (75), providing further rationale for longitudinal neurocognitive testing following postnatal ZIKV infection.…”

Microcatheter-assisted trabeculotomy versus rigid probe trabeculotomy in childhood glaucoma

“…Animal studies suggest an association between general anaesthesia and neurodevelopmental delay 20. Ophthalmologists with paediatric patients should be aware of the potentially life-threatening conditions associated with general anaesthesia.…”

Systematic review and meta-analysis comparing outcomes following orchidopexy for cryptorchidism before or after 1 year of age

“…Reasons cited for delaying surgery until boys are older than 12 months were concerns about possible increased rates of postoperative testicular atrophy in younger children and the heightened awareness of possible adverse effects on neurodevelopment of general anaesthesia in very young children. Much of the evidence about effects of anaesthesia on the developing brain come from animal studies; however, there is an increasing body of research investigating possible effects in humans19, 20, 21, 22.…”