Abulafia Ruth, Zalkind Vladimir, Devor Marshall
Department of Cell and Animal Biology, Institute of Life Sciences and Center for Research on Pain, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
J Neurosci. 2009 May 27;29(21):7053-64. doi: 10.1523/JNEUROSCI.1357-08.2009.
Microinjection of pentobarbital into a restricted region of rat brainstem, the mesopontine tegmental anesthesia area (MPTA), induces a reversible anesthesia-like state characterized by loss of the righting reflex, atonia, antinociception, and loss of consciousness as assessed by electroencephalogram synchronization. We examined cerebral activity during this state using FOS expression as a marker. Animals were anesthetized for 50 min with a series of intracerebral microinjections of pentobarbital or with systemic pentobarbital and intracerebral microinjections of vehicle. FOS expression was compared with that in awake animals microinjected with vehicle. Neural activity was suppressed throughout the cortex whether anesthesia was induced by systemic or MPTA routes. Changes were less consistent subcortically. In the zona incerta and the nucleus raphe pallidus, expression was strongly suppressed during systemic anesthesia, but only mildly during MPTA-induced anesthesia. Dissociation was seen in the tuberomammillary nucleus where suppression occurred during systemic-induced anesthesia only, and in the lateral habenular nucleus where activity was markedly increased during systemic-induced anesthesia but not following intracerebral microinjection. Several subcortical nuclei previously associated with cerebral arousal were not affected. In the MPTA itself FOS expression was suppressed during systemic anesthesia. Differences in the pattern of brain activity in the two modes of anesthesia are consistent with the possibility that anesthetic endpoints might be achieved by alternative mechanisms: direct drug action for systemic anesthesia or via ascending pathways for MPTA-induced anesthesia. However, it is also possible that systemically administered agents induce anesthesia, at least in part, by a primary action in the MPTA with cortical inhibition occurring secondarily.
将戊巴比妥微量注射到大鼠脑干的一个受限区域——中脑桥脑被盖麻醉区（MPTA），会诱导出一种可逆的麻醉样状态，其特征为翻正反射消失、肌张力缺失、抗伤害感受以及通过脑电图同步评估的意识丧失。我们使用FOS表达作为标志物来检查这种状态下的大脑活动。通过一系列戊巴比妥脑内微量注射或全身戊巴比妥联合脑内微量注射溶剂，将动物麻醉50分钟。将FOS表达与注射溶剂的清醒动物进行比较。无论麻醉是通过全身途径还是MPTA途径诱导，整个皮层的神经活动均受到抑制。皮层下的变化不太一致。在未定带和中缝苍白核中，全身麻醉期间表达强烈受抑制，但MPTA诱导麻醉期间仅轻度受抑制。在结节乳头核中出现分离现象，仅在全身诱导麻醉期间发生抑制，而在外侧缰核中，全身诱导麻醉期间活动明显增加，但脑内微量注射后则不然。几个先前与大脑觉醒相关的皮层下核未受影响。在全身麻醉期间，MPTA本身的FOS表达受到抑制。两种麻醉模式下大脑活动模式的差异与麻醉终点可能通过替代机制实现的可能性一致：全身麻醉通过直接药物作用，而MPTA诱导麻醉通过上行通路。然而，也有可能全身给药的药物至少部分是通过在MPTA中的主要作用诱导麻醉，随后发生皮层抑制。
