The GABAergic Parafacial Zone: Integrating Consciousness and Respiratory Control in Sevoflurane Anesthesia.

IF 9.1 1区医学 Q1 ANESTHESIOLOGY

Anesthesiology Pub Date : 2025-08-28 DOI:10.1097/ALN.0000000000005735

Linlin Luo, Zaixun Qin, Mei Chen, Yuanli Pi, Ying Wang, Zongcheng Jiang, Zhimin Deng, Jia Li, Xuejiao Dou, Junli Jiang, Haiying Wang, Shouyang Yu, Tian Yu, Tianyuan Luo

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引用次数: 0

Abstract

Background: General anesthesia induces both unconsciousness and respiratory depression, but whether these effects share a common neural substrate remains unclear. The parafacial zone (PZ), a GABAergic sleep-promoting region, has been proposed to modulate respiration. This study investigates whether PZ GABAergic neurons function as a common neural node coordinating anesthetic-induced unconsciousness and respiratory suppression.

Methods: A total of 95 male mice (10-12 weeks) were used. Chemogenetic and optogenetic methods targeted PZ GABAergic neurons to assess anesthetic efficacy and respiratory changes. Immunostaining evaluated neuronal activation, and awake-state stimulation tested for anesthesia-like effects.

Results: Chemogenetic activation of PZ GABAergic neurons enhanced anesthetic sensitivity, shifting the sevoflurane dose-response curve leftward (ED50: 0.662%, 95% CI: 0.624-0.699% vs. 1.569%, 95% CI: 1.502-1.637%) and lowering the concentration required for loss of righting reflex (0.735 ± 0.027% vs. 1.601 ± 0.048%, P < 0.0001, n = 10). Induction was faster (48 ± 4 s vs. 112 ± 3 s, P < 0.0001, n = 8) and emergence delayed (435 ± 12 s vs. 89 ± 12 s, P < 0.0001, n = 8). EEG showed increased delta and decreased theta power. Respiratory rate declined significantly (183 ± 24 bpm vs. 471 ± 3 bpm, P < 0.0001, n = 8). During anesthesia, brief optogenetic activation of PZ GABAergic neurons immediately elevated burst suppression ratio (69.5 ± 5.1% vs. 32.5 ± 7.7%, P < 0.0001, n = 9) and reduced respiratory rate (38 ± 13 bpm vs. 120 ± 21 bpm, P = 0.0016, n = 7), indicating concurrent modulation of cortical and respiratory function. Chemogenetic inhibition weakened anesthetic potency. Increased c-Fos expression in PZ GABAergic neurons during sevoflurane anesthesia confirmed their recruitment. In awake mice, optogenetic activation alone induced a low-arousal state with several features of anesthesia, including hypoactivity, analgesia, respiratory depression, and cortical suppression without abolishing righting reflex.

Conclusions: The GABAergic PZ is a shared critical node regulating both respiration and consciousness during sevoflurane anesthesia; its activation suppresses both, helping explain anesthesia-related respiratory depression.

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gaba能面旁区：七氟醚麻醉中意识与呼吸控制的整合。

背景：全身麻醉诱导无意识和呼吸抑制，但这些作用是否有共同的神经基质尚不清楚。旁面区（PZ）是一个gaba能促进睡眠的区域，已被提出调节呼吸。本研究探讨PZ gaba能神经元是否作为一个共同的神经节点协调麻醉诱导的无意识和呼吸抑制。方法：选取10 ~ 12周龄雄性小鼠95只。化学遗传学和光遗传学方法针对PZ gaba能神经元评估麻醉效果和呼吸变化。免疫染色评估神经元激活，清醒状态刺激测试麻醉样效果。结果：化学发生激活PZ gaba能神经元增强麻醉敏感性，使七氟烷剂量反应曲线左移（ED50: 0.662%, 95% CI: 0.624-0.699% vs. 1.569%, 95% CI: 1.502-1.637%），降低翻正反射丧失所需的浓度（0.735±0.027% vs. 1.601±0.048%,P < 0.0001, n = 10）。诱导更快（48±4 s比112±3 s， P < 0.0001, n = 8），出现延迟（435±12 s比89±12 s， P < 0.0001, n = 8）。脑电图显示波能量增加，波能量减少。呼吸频率明显下降（183±24 bpm比471±3 bpm， P < 0.0001, n = 8）。在麻醉过程中，PZ gaba能神经元的短暂光遗传激活立即提高了爆发抑制率（69.5±5.1% vs. 32.5±7.7%,P < 0.0001, n = 9），降低了呼吸速率（38±13 bpm vs. 120±21 bpm, P = 0.0016, n = 7），表明皮质和呼吸功能同时调节。化学发生抑制减弱了麻醉效力。七氟醚麻醉时PZ gaba能神经元c-Fos表达增加证实了它们的募集。在清醒的小鼠中，光遗传激活单独诱导低觉醒状态，具有麻醉的几个特征，包括低活动、镇痛、呼吸抑制和皮层抑制，但不消除翻正反射。结论：七氟醚麻醉时，gaba能PZ是调节呼吸和意识的共享关键节点；它的激活抑制了两者，有助于解释麻醉相关的呼吸抑制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anesthesiology 医学-麻醉学

CiteScore

10.40

自引率

5.70%

发文量

542

审稿时长

3-6 weeks

期刊介绍： With its establishment in 1940, Anesthesiology has emerged as a prominent leader in the field of anesthesiology, encompassing perioperative, critical care, and pain medicine. As the esteemed journal of the American Society of Anesthesiologists, Anesthesiology operates independently with full editorial freedom. Its distinguished Editorial Board, comprising renowned professionals from across the globe, drives the advancement of the specialty by presenting innovative research through immediate open access to select articles and granting free access to all published articles after a six-month period. Furthermore, Anesthesiology actively promotes groundbreaking studies through an influential press release program. The journal's unwavering commitment lies in the dissemination of exemplary work that enhances clinical practice and revolutionizes the practice of medicine within our discipline.