Khodaei Shahin, Wang Dian-Shi, Orser Beverley A
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Department of Anesthesiology & Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
BJA Open. 2023 May 30;6:100143. doi: 10.1016/j.bjao.2023.100143. eCollection 2023 Jun.
Inflammation and general anaesthesia likely contribute to perioperative neurocognitive disorders, possibly by causing a neuronal imbalance of excitation and inhibition. We showed previously that treatment with lipopolysaccharide (LPS) and sevoflurane causes a sustained increase in a tonic inhibitory conductance in the hippocampus; however, whether excitatory neurotransmission is also altered remains unknown. The goal of this study was to examine excitatory synaptic currents in the hippocampus after treatment with LPS and sevoflurane. Synaptic plasticity in the hippocampus, a cellular correlate of learning and memory, was also studied.
Mice were injected with vehicle or LPS (1 mg kg i.p.), and after 24 h they were then exposed to vehicle or sevoflurane (2.3%; 2 h). Hippocampal slices were prepared 48 h later. Excitatory synaptic currents were recorded from pyramidal neurones. Long-term potentiation (LTP) and long-term depression (LTD) were studied in the Schaffer collateral-cornu ammonis 1 pathway.
The amplitude of miniature excitatory postsynaptic currents (EPSCs) was reduced after LPS+sevoflurane (<0.001), whereas that of spontaneous EPSCs was unaltered, as evidenced by cumulative distribution plots. The frequency, area, and kinetics of both miniature and spontaneous EPSCs were unchanged, as were LTP and LTD.
The reduced amplitude of miniature EPSCs, coupled with the previously reported increase in tonic inhibition, indicates that the combination of LPS and sevoflurane markedly disrupts the balance of excitation and inhibition. Restoring this balance by pharmacologically enhancing excitatory neurotransmission and inhibiting the tonic current may represent an effective therapeutic option for perioperative neurocognitive disorders.
炎症和全身麻醉可能导致围手术期神经认知障碍，可能是通过引起神经元兴奋与抑制的失衡。我们之前表明，脂多糖（LPS）和七氟醚处理会导致海马体中强直抑制性电导持续增加；然而，兴奋性神经传递是否也发生改变仍不清楚。本研究的目的是检测LPS和七氟醚处理后海马体中的兴奋性突触电流。还研究了海马体中的突触可塑性，它是学习和记忆的细胞相关物。
给小鼠注射溶剂或LPS（腹腔注射1mg/kg），24小时后再将它们暴露于溶剂或七氟醚（2.3%；2小时）。48小时后制备海马体切片。从锥体神经元记录兴奋性突触电流。在Schaffer侧支-海马1通路中研究长时程增强（LTP）和长时程抑制（LTD）。
LPS+七氟醚处理后，微小兴奋性突触后电流（EPSCs）的幅度降低（<0.001），而自发EPSCs的幅度未改变，累积分布图证明了这一点。微小和自发EPSCs的频率、面积和动力学均未改变，LTP和LTD也是如此。
微小EPSCs幅度降低，加上先前报道的强直抑制增加，表明LPS和七氟醚的联合作用显著破坏了兴奋与抑制的平衡。通过药理学增强兴奋性神经传递和抑制强直电流来恢复这种平衡，可能是围手术期神经认知障碍的一种有效治疗选择。
