Wang Kui, Wei Haidong, Yang Liufei, Zhang Shuyue, Cheng Yiqin, Li Chen, Jia Pengyu, Zhang Yuanyuan, Zhang Yan, Fan Pei, Wang Ning, Lu Haixia, Chen Xinlin, Liu Yong, Zhang Pengbo
Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
Institute of Neurobiology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
Neuroscience. 2025 Jan 26;565:457-467. doi: 10.1016/j.neuroscience.2024.11.013. Epub 2024 Nov 13.
Sevoflurane impairs learning and memory of the developing brain. However, strategies to mitigate these detrimental effects have been scarce. Herein, we investigated whether tetramethylpyrazine pretreatment could alleviate the impairment of learning and memory and its underlying mechanism in sevoflurane-exposed neonatal rats. Postnatal 7-day Sprague-Dawley (SD) rats or primary hippocampal neurons were pretreated with tetramethylpyrazine and then exposed to sevoflurane. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and lactate dehydrogenase (LDH) assays were used to detect neuronal injury. Learning and memory function were evaluated by novel object recognition and Morris water maze tests. Long-term potentiation (LTP) was recorded to evaluate synaptic plasticity electrophysiologically in the hippocampal slices. Golgi-Cox staining or PSD95 immunochemistry was used to detect the morphology of dendritic spines. Western blotting was employed to assess the expressions of cleaved Caspase-3, PSD95, N-methyl-D-aspartate receptor (NMDAR) subunits NMDAR1, NMDAR2A and NMDAR2B in the hippocampus or cultured neurons. It was found that neonatal exposure of sevoflurane impaired learning and memory, increased neuronal apoptosis, altered the morphology of dendritic spines, upregulated the expressions of NMDAR2A and PSD95, and induced LTP deficits. Pretreatment with tetramethylpyrazine not only alleviated impairment of learning and memory, but also improved sevoflurane-induced changes in neuronal damage, dendritic spine morphology, NMDAR2A and PSD95 expressions, as well as LTP. These findings indicated that pretreatment with tetramethylpyrazine alleviated the impairment of learning and memory induced by sevoflurane through improvement of hippocampal synaptic plasticity in neonatal rats.
七氟醚会损害发育中大脑的学习和记忆能力。然而，减轻这些有害影响的策略却很匮乏。在此，我们研究了川芎嗪预处理是否能减轻七氟醚暴露新生大鼠的学习和记忆损伤及其潜在机制。出生后7天的斯普拉格-道利（SD）大鼠或原代海马神经元先用川芎嗪预处理，然后暴露于七氟醚。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）和乳酸脱氢酶（LDH）检测法检测神经元损伤。通过新物体识别和莫里斯水迷宫试验评估学习和记忆功能。记录长时程增强（LTP）以电生理方式评估海马切片中的突触可塑性。采用高尔基-考克斯染色或PSD95免疫化学检测树突棘的形态。采用蛋白质印迹法评估海马或培养神经元中裂解的半胱天冬酶-3、PSD95、N-甲基-D-天冬氨酸受体（NMDAR）亚基NMDAR1、NMDAR2A和NMDAR2B的表达。结果发现，新生大鼠暴露于七氟醚会损害学习和记忆，增加神经元凋亡，改变树突棘形态，上调NMDAR2A和PSD95的表达，并导致LTP缺陷。川芎嗪预处理不仅减轻了学习和记忆损伤，还改善了七氟醚诱导的神经元损伤、树突棘形态、NMDAR2A和PSD95表达以及LTP的变化。这些发现表明，川芎嗪预处理通过改善新生大鼠海马的突触可塑性减轻了七氟醚诱导的学习和记忆损伤。
