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Early-life single-episode sevoflurane exposure impairs social behavior and cognition later in life
Daisy Lin1, Jinyang Liu2, Lea Kramberg2
1Anesthesiology Department SUNY Downstate Medical Center Box 6, 450 Clarkson Ave Brooklyn New York 11203; Department of Physiology and Pharmacology SUNY Downstate Medical Center 450 Clarkson Ave Brooklyn New York 11203.
Insights
Single exposure to sevoflurane (sevo) anesthesia in neonatal mice impairs later-life learning, memory, and social behaviors. This study highlights the long-term neurodevelopmental effects of early-life anesthetic exposure.
Area of Science:
- Neuroscience
- Developmental Biology
- Anesthesiology
Background:
- Neonatal anesthetic exposure is common in young children undergoing surgery.
- The long-term effects of early-life anesthetics on brain development are not fully understood.
- Existing animal models often do not fully capture clinically relevant scenarios.
Purpose of the Study:
- To investigate the functional consequences of single-episode sevoflurane exposure on the developing brain.
- To assess long-term cognitive and behavioral changes following neonatal anesthesia.
- To provide a clinically relevant model for studying anesthetic effects on neurodevelopment.
Main Methods:
- Neonatal C57BL6 mice (postnatal day 7) were exposed to sevoflurane (2.38%) for 2 hours.
- Control mice received identical treatment without sevoflurane.
- Cognition and neuropsychiatric-like behaviors were assessed at 1-5 months of age using active place avoidance, novel object recognition, and social interaction tests.
Main Results:
- Sevoflurane-exposed mice exhibited deficits in learning and memory during periadolescence and adulthood.
- Reduced social interaction, including decreased interaction time with novel mice and social odors, was observed.
- The study identified significant behavioral changes indicative of social deficits post-anesthesia.
Conclusions:
- Single, 2-hour sevoflurane exposure in early life impairs cognitive function later in life.
- Neonatal sevoflurane administration can lead to neuropsychiatric-like behavioral changes, specifically social interaction deficits.
- This study elucidates the neurodevelopmental impact of a clinically relevant, single-episode anesthetic exposure during the neonatal period.
Background:
Single-episode anesthetic exposure is the most prevalent surgery-related incidence among young children in the United States. Although numerous studies have used animals to model the effects of neonatal anesthetics on behavioral changes later on in life, our understanding of the functional consequences to the developing brain in a comprehensive and clinically relevant manner is unclear.
Methods:
The volatile anesthetic, sevoflurane (sevo) was administered to C57BL6 postnatal day 7 (P7) mice in a 40% oxygen and 60% nitrogen gas mixture. In order to examine the effects of sevo alone on the developing brain in a clinically relevant manner, mice were exposed to an average of 2.38 ± 0.11% sevo for 2 h. No sevo (control) mice were treated in an identical manner without sevo exposure. Mice were examined for cognition and neuropsychiatric-like behavioral changes at 1-5 months of age.
Results:
Using the active place avoidance (APA) test and the novel object recognition (NOR) test, we demonstrated that P7 sevo-treated mice showed a deficit in learning and memory both during periadolescence and adulthood. We then employed a battery of neuropsychiatric-like behavioral tests to examine social interaction, communication, and repetitive behavior. Interestingly, compared to the no-sevo-treated group, sevo-treated mice showed significant reductions in the time interacting with a novel mouse (push-crawl and following), time and interaction in a chamber with a novel mouse, and time sniffing a novel social odor.
Conclusions:
Our study established that single-episode, 2-h sevo treatment during early life impairs cognition later on in life. With this approach, we also observed neuropsychiatric-like behavior changes such as social interaction deficits in the sevo-treated mice. This study elucidated the effects of a clinically relevant single-episode sevo application, given during the neonatal period, on neurodevelopmental behavioral changes later on in life.
