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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.


Related in: MedlinePlus

Neonatal sevo treatment impaired learning and memory during periadolescence. (A) Locomotion of a no‐sevo‐ and a sevo‐treated mouse are represented by traces on the circular rotating platform. The arrow indicates the direction of platform movement (1 revolution per minute). Entrances into the shock zone (represented by the 60° red zone) are marked as the red dots. (B) At P27 and P28, sevo‐treated mice entered the shock zone significantly more compared to the no‐sevo–treated group during a total of 10 trials. Two‐way ANOVA was used for statistical calculation: F(1, 63) = 1.28, P < 0.01 for treatment; F(9, 63) = 14.6, P < 0.001 for trials; F(9, 63) = 1.8, P > 0.05 for interaction between treatment and trials. Bonferroni posttests showed P < 0.05 for treatment on day 1, trials 4 and 5; day 2, trial 2. Asterisk (*) denotes P < 0.05 for treatment effect within the trials (N = 4 for no sevo, N = 5 for sevo).
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brb3514-fig-0003: Neonatal sevo treatment impaired learning and memory during periadolescence. (A) Locomotion of a no‐sevo‐ and a sevo‐treated mouse are represented by traces on the circular rotating platform. The arrow indicates the direction of platform movement (1 revolution per minute). Entrances into the shock zone (represented by the 60° red zone) are marked as the red dots. (B) At P27 and P28, sevo‐treated mice entered the shock zone significantly more compared to the no‐sevo–treated group during a total of 10 trials. Two‐way ANOVA was used for statistical calculation: F(1, 63) = 1.28, P < 0.01 for treatment; F(9, 63) = 14.6, P < 0.001 for trials; F(9, 63) = 1.8, P > 0.05 for interaction between treatment and trials. Bonferroni posttests showed P < 0.05 for treatment on day 1, trials 4 and 5; day 2, trial 2. Asterisk (*) denotes P < 0.05 for treatment effect within the trials (N = 4 for no sevo, N = 5 for sevo).

Mentions: We observed learning and memory impairment as early as periadolescent age (P27 and P28), based on the hippocampus‐dependent APA test. The mouse learned to avoid a stationary shock zone in a constant rotating arena using the distal room landmarks as cues (Fig. 3). The no‐sevo–treated mice learned to avoid the shock zone over five trials during day 1 and this behavior persisted into day 2. A similar observation was not present in the sevo group. Sevo‐treated mice showed significantly more entrances into the shock zone over the 2 days, 10‐trial period (two‐way ANOVA followed by Bonferroni posttests, P < 0.01 for treatment, P < 0.001 for trial, P > 0.05 for interaction between treatment and trial, and P < 0.05 for treatment effect within trials, day 1—trials 4 and 5 and day 2—trial 2).


Early ‐ life single ‐ episode sevoflurane exposure impairs social behavior and cognition later in life
Neonatal sevo treatment impaired learning and memory during periadolescence. (A) Locomotion of a no‐sevo‐ and a sevo‐treated mouse are represented by traces on the circular rotating platform. The arrow indicates the direction of platform movement (1 revolution per minute). Entrances into the shock zone (represented by the 60° red zone) are marked as the red dots. (B) At P27 and P28, sevo‐treated mice entered the shock zone significantly more compared to the no‐sevo–treated group during a total of 10 trials. Two‐way ANOVA was used for statistical calculation: F(1, 63) = 1.28, P < 0.01 for treatment; F(9, 63) = 14.6, P < 0.001 for trials; F(9, 63) = 1.8, P > 0.05 for interaction between treatment and trials. Bonferroni posttests showed P < 0.05 for treatment on day 1, trials 4 and 5; day 2, trial 2. Asterisk (*) denotes P < 0.05 for treatment effect within the trials (N = 4 for no sevo, N = 5 for sevo).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036436&req=5

brb3514-fig-0003: Neonatal sevo treatment impaired learning and memory during periadolescence. (A) Locomotion of a no‐sevo‐ and a sevo‐treated mouse are represented by traces on the circular rotating platform. The arrow indicates the direction of platform movement (1 revolution per minute). Entrances into the shock zone (represented by the 60° red zone) are marked as the red dots. (B) At P27 and P28, sevo‐treated mice entered the shock zone significantly more compared to the no‐sevo–treated group during a total of 10 trials. Two‐way ANOVA was used for statistical calculation: F(1, 63) = 1.28, P < 0.01 for treatment; F(9, 63) = 14.6, P < 0.001 for trials; F(9, 63) = 1.8, P > 0.05 for interaction between treatment and trials. Bonferroni posttests showed P < 0.05 for treatment on day 1, trials 4 and 5; day 2, trial 2. Asterisk (*) denotes P < 0.05 for treatment effect within the trials (N = 4 for no sevo, N = 5 for sevo).
Mentions: We observed learning and memory impairment as early as periadolescent age (P27 and P28), based on the hippocampus‐dependent APA test. The mouse learned to avoid a stationary shock zone in a constant rotating arena using the distal room landmarks as cues (Fig. 3). The no‐sevo–treated mice learned to avoid the shock zone over five trials during day 1 and this behavior persisted into day 2. A similar observation was not present in the sevo group. Sevo‐treated mice showed significantly more entrances into the shock zone over the 2 days, 10‐trial period (two‐way ANOVA followed by Bonferroni posttests, P < 0.01 for treatment, P < 0.001 for trial, P > 0.05 for interaction between treatment and trial, and P < 0.05 for treatment effect within trials, day 1—trials 4 and 5 and day 2—trial 2).

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.


Related in: MedlinePlus