Background Sevoflurane is a volatile anesthetic that is widely used in pediatric anesthesia due to its low toxicity. However, whether neonatal exposure to sevoflurane induces long-lasting cognitive impairment remains unclear. It has reported that neuronal injury is the main cause of sevoflurane induced learning and memory disabilities in the development of brain. But the specific mechanism is not well elucidated. The injury of synapse occurs earlier than neuronal cell in brain injury. The function synaptic plasticity is involved in learning and memory. Methods We compared the learning and memory ability of of neonatal mice to sevoflurane for once or three times in vitro and synaptic plasticity, as well as neuronal excitability in vivo. In this study, neonatal C57BL/J mice were exposed to 3% sevoflurane for 2 h on postnatal day 7 (P7) or once daily for 3 consecutive days (P7/8/9). Morris water maze (MWM) test was performed to evaluate the cognitive performance on P31 and P61, respectively. Theta burst stimulation-induced long-term potentiation (LTP) was measured in acute hippocampal slices from P38 and P68 mice to assess the synaptic plasticity. Primary hippocampal neurons were isolated from 24 h-old mice and exposed to different doses of sevoflurane (1, 2, and 3 MAC) for 6 h to examine the neuronal excitability. Results The results showed that compared with control, repeated exposure to sevoflurane resulted in significant cognitive impairment in adolescent mice while showing no effect on adult mice. Repeated exposure to sevoflurane remarkably attenuated hippocampal LTP of adolescent mice, which turned to normal in adult mice. No significant difference of LTP was observed between control mice and one-dose sevoflurane-treated mice both in adolescent and adult mice. In primary hippocampal neurons, 2 MAC and 3 MAC sevoflurane delayed neuronal excitation and dose-dependently reduced the number of evoked action potentials compared with control. These effects disappeared after a 24-h recovery. Conclusions These data suggested that sevoflurane may impair cognitive performance and neuronal plasticity when administered repeatedly or in a high MAC during infancy, which is noticeable during adolescence but alleviates during adulthood.

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Xiaoyan Zhao et al.
Developmental Neuroscience February 2022