Abstract
Millions of children undergo general anesthesia each year, and animal and human studies have indicated that exposure to anesthesia at an early age can impact neuronal development, leading to behavioral and learning impairments that manifest later in childhood and adolescence. Here, we examined the effects of isoflurane, a commonly-used general anesthetic, which was delivered to newborn rabbits. Trace eyeblink classical conditioning was used to assess the impact of neonatal anesthesia exposure on behavioral learning in adolescent subjects, and a variety of MRI techniques including fMRI, MR volumetry, spectroscopy and DTI captured functional, metabolic, and structural changes in key regions of the learning and sensory systems associated with anesthesia-induced learning impairment. Our results demonstrated a wide array of changes that were specific to anesthesia-exposed subjects, which supports previous studies that have pointed to a link between early anesthesia exposure and the development of learning and behavioral deficiencies. These findings point to the need for caution in avoiding excessive use of general anesthesia in young children and neonates.
Highlights
Millions of children undergo general anesthesia each year, and animal and human studies have indicated that exposure to anesthesia at an early age can impact neuronal development, leading to behavioral and learning impairments that manifest later in childhood and adolescence
A conditioned responses (CR) is an automatic response in response to a neutral stimulus. This whisker vibration is the conditioned stimulus (CS), which occurs before the airpuff, which served as the unconditioned stimulus (US)
Analysis of learning levels for each session using one-way ANOVA found that a difference between the control and anesthesia-exposed groups first appeared at session 7, when the mean CRs was 43.2 ± 14.6% for the control, 9.8 ± 5.1 for anesthesia in air (IA) group, and 2.5 ± 1.5% for anesthesia in 80% oxygen (IO) group (p < 0.019, F = 5.5, df = 2)
Summary
Millions of children undergo general anesthesia each year, and animal and human studies have indicated that exposure to anesthesia at an early age can impact neuronal development, leading to behavioral and learning impairments that manifest later in childhood and adolescence. Our results demonstrated a wide array of changes that were specific to anesthesia-exposed subjects, which supports previous studies that have pointed to a link between early anesthesia exposure and the development of learning and behavioral deficiencies. These findings point to the need for caution in avoiding excessive use of general anesthesia in young children and neonates. We assessed the impact of anesthesia 3 months after exposure, which is approximately
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