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Early ‐ life single ‐ episode sevoflurane exposure impairs social behavior and cognition later in life

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Neonatal sevo‐treated mice had a deficiency in social interaction behaviors as shown by reciprocal social interaction. (A) The sevo‐treated mice showed significantly less push–crawl and following toward a novel mouse of the same sex and similar age compared to the no‐sevo–treated mice. (B–D) During the 10 min of the reciprocal social interaction paradigm, the two groups of mice did not display a difference in arena exploration, self‐grooming, or total time being mobile in the cage. Unpaired t‐test with Welch's correction was used for statistical calculation. Asterisk (*) denotes P < 0.05 (N = 18 for no sevo; N = 17 for sevo).
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brb3514-fig-0005: Neonatal sevo‐treated mice had a deficiency in social interaction behaviors as shown by reciprocal social interaction. (A) The sevo‐treated mice showed significantly less push–crawl and following toward a novel mouse of the same sex and similar age compared to the no‐sevo–treated mice. (B–D) During the 10 min of the reciprocal social interaction paradigm, the two groups of mice did not display a difference in arena exploration, self‐grooming, or total time being mobile in the cage. Unpaired t‐test with Welch's correction was used for statistical calculation. Asterisk (*) denotes P < 0.05 (N = 18 for no sevo; N = 17 for sevo).

Mentions: We scored the four most predominant behaviors of the subject mouse while paired with the target mouse in the novel cage, such as push–crawl/following, arena exploration, self‐grooming, and time being mobile. Among the four measurements, sevo‐treated mice showed a specific deficit compared to no‐sevo–treated mice on the amount of time they engage in push–crawling and following the unfamiliar mouse (Fig. 5; unpaired t‐test with Welch's correction, P < 0.05). Data show mice exposed to single‐episode sevo treatment on P7 had impaired social interaction later on in life.


Early ‐ life single ‐ episode sevoflurane exposure impairs social behavior and cognition later in life
Neonatal sevo‐treated mice had a deficiency in social interaction behaviors as shown by reciprocal social interaction. (A) The sevo‐treated mice showed significantly less push–crawl and following toward a novel mouse of the same sex and similar age compared to the no‐sevo–treated mice. (B–D) During the 10 min of the reciprocal social interaction paradigm, the two groups of mice did not display a difference in arena exploration, self‐grooming, or total time being mobile in the cage. Unpaired t‐test with Welch's correction was used for statistical calculation. Asterisk (*) denotes P < 0.05 (N = 18 for no sevo; N = 17 for sevo).
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Related In: Results  -  Collection

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brb3514-fig-0005: Neonatal sevo‐treated mice had a deficiency in social interaction behaviors as shown by reciprocal social interaction. (A) The sevo‐treated mice showed significantly less push–crawl and following toward a novel mouse of the same sex and similar age compared to the no‐sevo–treated mice. (B–D) During the 10 min of the reciprocal social interaction paradigm, the two groups of mice did not display a difference in arena exploration, self‐grooming, or total time being mobile in the cage. Unpaired t‐test with Welch's correction was used for statistical calculation. Asterisk (*) denotes P < 0.05 (N = 18 for no sevo; N = 17 for sevo).
Mentions: We scored the four most predominant behaviors of the subject mouse while paired with the target mouse in the novel cage, such as push–crawl/following, arena exploration, self‐grooming, and time being mobile. Among the four measurements, sevo‐treated mice showed a specific deficit compared to no‐sevo–treated mice on the amount of time they engage in push–crawling and following the unfamiliar mouse (Fig. 5; unpaired t‐test with Welch's correction, P < 0.05). Data show mice exposed to single‐episode sevo treatment on P7 had impaired social interaction later on in life.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Single&#8208;episode anesthetic exposure is the most prevalent surgery&#8208;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&nbsp;&plusmn;&nbsp;0.11% sevo for 2&nbsp;h. No sevo (control) mice were treated in an identical manner without sevo exposure. Mice were examined for cognition and neuropsychiatric&#8208;like behavioral changes at 1&ndash;5&nbsp;months of age.

Results: Using the active place avoidance (APA) test and the novel object recognition (NOR) test, we demonstrated that P7 sevo&#8208;treated mice showed a deficit in learning and memory both during periadolescence and adulthood. We then employed a battery of neuropsychiatric&#8208;like behavioral tests to examine social interaction, communication, and repetitive behavior. Interestingly, compared to the no&#8208;sevo&ndash;treated group, sevo&#8208;treated mice showed significant reductions in the time interacting with a novel mouse (push&ndash;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&#8208;episode, 2&#8208;h sevo treatment during early life impairs cognition later on in life. With this approach, we also observed neuropsychiatric&#8208;like behavior changes such as social interaction deficits in the sevo&#8208;treated mice. This study elucidated the effects of a clinically relevant single&#8208;episode sevo application, given during the neonatal period, on neurodevelopmental behavioral changes later on in life.

No MeSH data available.