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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‐treated mice showed impairment in learning and memory during adulthood. (A) A schematic layout of the novel object recognition task that was used to examine the learning and memory behavior in mice. (B) During day 1—familiarization, both no sevo and sevo groups spent similar amounts of time exploring the two identical objects. No preference for a specific object was detected. A two‐way ANOVA was used for statistical analysis, P > 0.05 for treatment, object, and interaction between treatment and object. (C) During day 2—testing, while the no‐sevo–treated group spent significantly more time exploring the novel object, the sevo‐treated group did not show an increased interest. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 36) = 3.6, P > 0.05 for treatment; F(1, 36) = 10.4, P < 0.01 for object; F(1, 36) = 3.6, P > 0.05 for interaction between treatment and object. Asterisk (**) denotes P < 0.01 for exploration time between the two different objects in the no sevo group (N = 11 for no sevo; N = 9 for sevo).
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brb3514-fig-0004: Neonatal sevo‐treated mice showed impairment in learning and memory during adulthood. (A) A schematic layout of the novel object recognition task that was used to examine the learning and memory behavior in mice. (B) During day 1—familiarization, both no sevo and sevo groups spent similar amounts of time exploring the two identical objects. No preference for a specific object was detected. A two‐way ANOVA was used for statistical analysis, P > 0.05 for treatment, object, and interaction between treatment and object. (C) During day 2—testing, while the no‐sevo–treated group spent significantly more time exploring the novel object, the sevo‐treated group did not show an increased interest. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 36) = 3.6, P > 0.05 for treatment; F(1, 36) = 10.4, P < 0.01 for object; F(1, 36) = 3.6, P > 0.05 for interaction between treatment and object. Asterisk (**) denotes P < 0.01 for exploration time between the two different objects in the no sevo group (N = 11 for no sevo; N = 9 for sevo).

Mentions: We examined cognitive function of adult mice (ages 4–5 months) by the NOR test. The NOR is a widely used learning and memory task, which offers no external stimuli or reinforcement (Leger et al. 2013). During day 1—familiarization (Fig. 4A), both the no‐sevo‐ and sevo‐treated groups spent a similar amount of time exploring the two identical objects, with no differential preference for a specific object (Fig. 4B; two‐way ANOVA). However, during day 2—testing (Fig. 4A), the no sevo group spent significantly more time exploring the novel object; this difference was not found in the sevo‐treated group (Fig. 4C; two‐way ANOVA, followed by Bonferroni posttests, P < 0.01 for time exploring the objects in the no sevo group). Combining the two sets of learning and memory behavioral tests, data demonstrated for the first time, a 2‐h, single‐episode neonatal exposure to less than one MAC of sevo impairs learning and memory as early as periadolescence and this persists to adulthood.


Early ‐ life single ‐ episode sevoflurane exposure impairs social behavior and cognition later in life
Neonatal sevo‐treated mice showed impairment in learning and memory during adulthood. (A) A schematic layout of the novel object recognition task that was used to examine the learning and memory behavior in mice. (B) During day 1—familiarization, both no sevo and sevo groups spent similar amounts of time exploring the two identical objects. No preference for a specific object was detected. A two‐way ANOVA was used for statistical analysis, P > 0.05 for treatment, object, and interaction between treatment and object. (C) During day 2—testing, while the no‐sevo–treated group spent significantly more time exploring the novel object, the sevo‐treated group did not show an increased interest. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 36) = 3.6, P > 0.05 for treatment; F(1, 36) = 10.4, P < 0.01 for object; F(1, 36) = 3.6, P > 0.05 for interaction between treatment and object. Asterisk (**) denotes P < 0.01 for exploration time between the two different objects in the no sevo group (N = 11 for no sevo; N = 9 for sevo).
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brb3514-fig-0004: Neonatal sevo‐treated mice showed impairment in learning and memory during adulthood. (A) A schematic layout of the novel object recognition task that was used to examine the learning and memory behavior in mice. (B) During day 1—familiarization, both no sevo and sevo groups spent similar amounts of time exploring the two identical objects. No preference for a specific object was detected. A two‐way ANOVA was used for statistical analysis, P > 0.05 for treatment, object, and interaction between treatment and object. (C) During day 2—testing, while the no‐sevo–treated group spent significantly more time exploring the novel object, the sevo‐treated group did not show an increased interest. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 36) = 3.6, P > 0.05 for treatment; F(1, 36) = 10.4, P < 0.01 for object; F(1, 36) = 3.6, P > 0.05 for interaction between treatment and object. Asterisk (**) denotes P < 0.01 for exploration time between the two different objects in the no sevo group (N = 11 for no sevo; N = 9 for sevo).
Mentions: We examined cognitive function of adult mice (ages 4–5 months) by the NOR test. The NOR is a widely used learning and memory task, which offers no external stimuli or reinforcement (Leger et al. 2013). During day 1—familiarization (Fig. 4A), both the no‐sevo‐ and sevo‐treated groups spent a similar amount of time exploring the two identical objects, with no differential preference for a specific object (Fig. 4B; two‐way ANOVA). However, during day 2—testing (Fig. 4A), the no sevo group spent significantly more time exploring the novel object; this difference was not found in the sevo‐treated group (Fig. 4C; two‐way ANOVA, followed by Bonferroni posttests, P < 0.01 for time exploring the objects in the no sevo group). Combining the two sets of learning and memory behavioral tests, data demonstrated for the first time, a 2‐h, single‐episode neonatal exposure to less than one MAC of sevo impairs learning and memory as early as periadolescence and this persists to adulthood.

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