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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.


Two approaches of sevo treatment on postnatal day 7 (P7) mice. (A) The approximate minimum alveolar concentration (MAC) of sevo necessary for P7 mice was established by tail clamping every 10 min during treatment. The approximate MAC of sevo was averaged to be 3.58 ± 0.07% based on the concentration recorded every 5 min (N = 13). (B) On a separate group of mice, less than one MAC (2.38 ± 0.11%) of sevo was given without tail clamping. This group of mice was then used in all the subsequent behavior paradigms (N = 17). (C and D) Data shown are measurements taken from the group of mice that were exposed to sevo with tail clamp. SpO2 and heart rate were recorded every 5 min on all mice undergoing sevo treatment.
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brb3514-fig-0001: Two approaches of sevo treatment on postnatal day 7 (P7) mice. (A) The approximate minimum alveolar concentration (MAC) of sevo necessary for P7 mice was established by tail clamping every 10 min during treatment. The approximate MAC of sevo was averaged to be 3.58 ± 0.07% based on the concentration recorded every 5 min (N = 13). (B) On a separate group of mice, less than one MAC (2.38 ± 0.11%) of sevo was given without tail clamping. This group of mice was then used in all the subsequent behavior paradigms (N = 17). (C and D) Data shown are measurements taken from the group of mice that were exposed to sevo with tail clamp. SpO2 and heart rate were recorded every 5 min on all mice undergoing sevo treatment.

Mentions: In order to understand the effect that neonatal sevo treatment alone has on behavioral changes later on in life, we established two different sevo treatment groups. During a 2‐h treatment period, we used tail clamp to first establish that the approximate MAC of sevo for P7 mice averaged 3.58 ± 0.07% (Fig. 1A). Since tail clamp may result in pain and scaring of the tail similar to the act of clinical surgery, we then treated a separate group of mice in a similar manner but without tail clamp. This second group of mice was treated with a reduced concentration of sevo, which was sufficient to keep the mice immobilized/unconscious and this sevo concentration averaged 2.38 ± 0.11% (Fig. 1B). These mice were subsequently examined for the effect of neonatal sevo treatment alone on behavioral changes later on in life. Mice were monitored closely for their measurements of peripheral capillary oxygen saturation (SpO2) and HR during the treatment. An average SpO2 of 97 ± 0.11% and HR of 427 ± 2.02 beats per min suggest the mice were in a physiological healthy state, without any signs of hypoxia (Fig. 1C and D).


Early ‐ life single ‐ episode sevoflurane exposure impairs social behavior and cognition later in life
Two approaches of sevo treatment on postnatal day 7 (P7) mice. (A) The approximate minimum alveolar concentration (MAC) of sevo necessary for P7 mice was established by tail clamping every 10 min during treatment. The approximate MAC of sevo was averaged to be 3.58 ± 0.07% based on the concentration recorded every 5 min (N = 13). (B) On a separate group of mice, less than one MAC (2.38 ± 0.11%) of sevo was given without tail clamping. This group of mice was then used in all the subsequent behavior paradigms (N = 17). (C and D) Data shown are measurements taken from the group of mice that were exposed to sevo with tail clamp. SpO2 and heart rate were recorded every 5 min on all mice undergoing sevo treatment.
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brb3514-fig-0001: Two approaches of sevo treatment on postnatal day 7 (P7) mice. (A) The approximate minimum alveolar concentration (MAC) of sevo necessary for P7 mice was established by tail clamping every 10 min during treatment. The approximate MAC of sevo was averaged to be 3.58 ± 0.07% based on the concentration recorded every 5 min (N = 13). (B) On a separate group of mice, less than one MAC (2.38 ± 0.11%) of sevo was given without tail clamping. This group of mice was then used in all the subsequent behavior paradigms (N = 17). (C and D) Data shown are measurements taken from the group of mice that were exposed to sevo with tail clamp. SpO2 and heart rate were recorded every 5 min on all mice undergoing sevo treatment.
Mentions: In order to understand the effect that neonatal sevo treatment alone has on behavioral changes later on in life, we established two different sevo treatment groups. During a 2‐h treatment period, we used tail clamp to first establish that the approximate MAC of sevo for P7 mice averaged 3.58 ± 0.07% (Fig. 1A). Since tail clamp may result in pain and scaring of the tail similar to the act of clinical surgery, we then treated a separate group of mice in a similar manner but without tail clamp. This second group of mice was treated with a reduced concentration of sevo, which was sufficient to keep the mice immobilized/unconscious and this sevo concentration averaged 2.38 ± 0.11% (Fig. 1B). These mice were subsequently examined for the effect of neonatal sevo treatment alone on behavioral changes later on in life. Mice were monitored closely for their measurements of peripheral capillary oxygen saturation (SpO2) and HR during the treatment. An average SpO2 of 97 ± 0.11% and HR of 427 ± 2.02 beats per min suggest the mice were in a physiological healthy state, without any signs of hypoxia (Fig. 1C and D).

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.