BACKGROUND: Orexin, a neuropeptide derived from the perifornical area of the hypothalamus (PeFLH), promotes the recovery of propofol, isoflurane, and sevoflurane anesthesias, without influencing the induction time. However, whether the orexinergic system also plays a similar role in desflurane anesthesia, which is widely applied in clinical practice owing to its most rapid onset and offset time among all volatile anesthetics, has not yet been studied. In the present study, we explored the effect of the orexinergic system on the consciousness state induced by desflurane anesthesia. METHODS: The c-Fos staining was used to observe the activity changes of orexinergic neurons in the PeFLH and their efferent projection regions under desflurane anesthesia. Chemogenetic and optogenetic techniques were applied to compare the effect of PeFLH orexinergic neurons on the induction, emergence, and maintenance states between desflurane and isoflurane anesthesias. Orexinergic terminals in the paraventricular thalamic nucleus (PVT) were manipulated with pharmacologic, chemogenetic, and optogenetic techniques to assess the effect of orexinergic circuitry on desflurane anesthesia. RESULTS: Desflurane anesthesia inhibited the activity of orexinergic neurons in the PeFLH, as well as the neuronal activity in PVT, basal forebrain, dorsal raphe nucleus, and ventral tegmental area, as demonstrated by c-Fos staining. Activation of PeFLH orexinergic neurons prolonged the induction time and accelerated emergence from desflurane anesthesia but only influenced the emergence in isoflurane anesthesia, as demonstrated by chemogenetic and pharmacologic techniques. Meanwhile, optical activation of orexinergic neurons exhibited a long-lasting inhibitory effect on burst-suppression ratio (BSR) under desflurane anesthesia, and the effect may be contributed by the orexinergic PeFLH-PVT circuitry. The orexin-2 receptor (OX2R), but not orexin-1 receptor (OX1R), in the PVT, which had been inhibited most significantly by desflurane, mediated the proemergence effect of desflurane anesthesia. CONCLUSIONS: We discovered, for the first time, that orexinergic neurons in the PeFLH could not only influence the maintenance and emergence from isoflurane and desflurane anesthesias but also affect the induction under desflurane anesthesia. Furthermore, this specific effect is probably mediated by orexinergic PeFLH-PVT circuitry, especially OX2Rs in the PVT.

中文翻译：

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激活食欲神经元抑制地氟醚麻醉对大鼠脑室旁丘脑核意识状态的影响

背景：食欲素是一种来源于下丘脑眶周区 (PeFLH) 的神经肽，可促进丙泊酚、异氟醚和七氟醚麻醉的恢复，而不影响诱导时间。然而，地氟醚麻醉在所有挥发性麻醉剂中起效和抵消时间最快，在临床实践中得到广泛应用，但食欲素能系统是否也发挥类似作用尚未研究。在本研究中，我们探讨了食欲系统对地氟醚麻醉诱导的意识状态的影响。方法：采用c-Fos染色法观察地氟醚麻醉下PeFLH及其传出投射区食欲素能神经元的活性变化。应用化学遗传学和光遗传学技术来比较 PeFLH 食欲神经元对地氟醚和异氟醚麻醉之间的诱导、出现和维持状态的影响。使用药理学、化学遗传学和光遗传学技术处理室旁丘脑核 (PVT) 中的食欲素末端，以评估食欲素回路对地氟醚麻醉的影响。结果：地氟醚麻醉抑制了 PeFLH 中食欲素能神经元的活动，以及 PVT、基底前脑、中缝背核和腹侧被盖区的神经元活动，如 c-Fos 染色所示。PeFLH 食欲神经元的激活延长了诱导时间并加速了地氟醚麻醉的苏醒，但仅影响了异氟醚麻醉的苏醒，正如化学遗传学和药理学技术所证明的那样。同时，在地氟醚麻醉下，食欲素能神经元的光激活对爆发抑制比（BSR）表现出持久的抑制作用，该效应可能是由食欲素能 PeFLH-PVT 电路造成的。地氟醚抑制最显着的 PVT 中的食欲素 2 受体 (OX2R)，而不是食欲素-1 受体 (OX1R)，介导了地氟醚麻醉的出苗前效应。结论：我们首次发现PeFLH中的食欲神经元不仅可以影响异氟醚和地氟醚麻醉的维持和苏醒，还可以影响地氟醚麻醉下的诱导。此外，这种特殊效应可能是由食欲素 PeFLH-PVT 电路介导的，尤其是 PVT 中的 OX2R。