Abstract
Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures.
Highlights
Previous retrospective studies suggested that children, who had undergone multiple anesthesia and surgeries at an earlier age, were more likely to develop learning disability in future [1, 2]
We investigated whether multiple sevoflurane exposures impaired the synaptogenesis in the developing brain and detected expressions of synapse makers PSD95 and synaptophysin in the hippocampus after three exposures of 3% sevoflurane
There were significant differences between sevoflurane group and control group (Figure 1(c), P = 0.0020; Figure 1(d), P = 0.0009). These results indicated that multiple sevoflurane exposures induced synaptogenesis impairment in the hippocampus
Summary
Previous retrospective studies suggested that children, who had undergone multiple anesthesia and surgeries at an earlier age, were more likely to develop learning disability in future [1, 2]. The studies from neonatal rodents or primates demonstrated that a majority of general anesthetics had the potential to induce neurotoxicity in the developing brain [3, 4]. Sevoflurane, one of inhalational anesthetics, is commonly used in pediatric anesthesia for its better tolerance and excellent anesthetic effects. Multiple sevoflurane exposures, during brain development period, impaired synaptogenesis and cause severe cognitive decline [5, 6]. Despite extensive studies about the mechanisms by which sevoflurane induced developmental neurotoxicity, there were very rare researches on the methods to reverse it. During embryonic and postnatal period, DHA plays an important role in the neural development [8]. The present study investigates whether DHA rectifies the synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures
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