Sun Zhongliang, Satomoto Maiko, Adachi Yushi U, Makita Koshi
Department of Anesthesiology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Anesthesiology, Graduate School of Medicine, Nagoya University, Aichi, Japan.
Korean J Anesthesiol. 2017 Jun;70(3):335-340. doi: 10.4097/kjae.2017.70.3.335. Epub 2017 Apr 21.
Neonatal exposure to anesthetics induces neuronal apoptosis and long-term cognitive dysfunction in rodents. We showed that the nicotinamide adenine dinucleotide phosphate-oxidase inhibitor apocynin not only reduces neurotoxicity by decreasing superoxide levels and preventing mitochondrial dysfunction but also improves long-term memory impairment in neonatal mice exposed to sevoflurane. We also found that after the contextual fear conditioning test, glutamatergic neurons expressed c-Fos (neural activation) regardless of previous exposure to sevoflurane. Moreover, there were fewer c-Fos-expressing glutamatergic neurons in the basolateral amygdala (BLA) after exposure to sevoflurane than after exposure to carrier gas. In this study, we investigated whether the administration of apocynin prior to sevoflurane exposure would preserve glutamatergic neurons in the BLA.
Apocynin (50 mg/kg) was injected intraperitoneally into six-day-old male mice 30 min before 6 h of exposure to 3% sevoflurane or carrier gas only. The mice were allowed to mature and then were subjected to the contextual fear conditioning test. The neural activation and neuron population in the BLA were investigated 2 h later.
Administration of apocynin prior to neonatal sevoflurane exposure not only prevented learning deficits but also preserved c-Fos-expressing glutamatergic neurons in the BLA.
Apocynin mitigates the cognitive impairment induced by neonatal sevoflurane exposure and preserves c-Fos-expressing glutamatergic neurons in the basolateral amygdala.
新生鼠暴露于麻醉剂会诱导神经元凋亡并导致长期认知功能障碍。我们发现烟酰胺腺嘌呤二核苷酸磷酸氧化酶抑制剂阿朴吗啡不仅通过降低超氧化物水平和预防线粒体功能障碍来降低神经毒性，还能改善暴露于七氟醚的新生小鼠的长期记忆损伤。我们还发现，在情境恐惧条件反射试验后，无论之前是否暴露于七氟醚，谷氨酸能神经元都会表达c-Fos（神经激活）。此外，暴露于七氟醚后，基底外侧杏仁核（BLA）中表达c-Fos的谷氨酸能神经元比暴露于载气后更少。在本研究中，我们调查了在暴露于七氟醚之前给予阿朴吗啡是否能保护BLA中的谷氨酸能神经元。
在6日龄雄性小鼠暴露于3%七氟醚或仅载气6小时前30分钟，腹腔注射阿朴吗啡（50 mg/kg）。让小鼠成熟，然后进行情境恐惧条件反射试验。2小时后调查BLA中的神经激活和神经元数量。
新生鼠暴露于七氟醚之前给予阿朴吗啡不仅预防了学习缺陷，还保护了BLA中表达c-Fos的谷氨酸能神经元。
阿朴吗啡减轻了新生鼠暴露于七氟醚引起的认知损伤，并保护了基底外侧杏仁核中表达c-Fos的谷氨酸能神经元。
