Between Clotho and Lachesis: how isoflurane seals neuronal fate.
Between Clotho and Lachesis: how isoflurane seals neuronal fate.
复制标题
克洛托和拉克西斯之间：异氟烷如何决定神经元的命运。
DOI：
10.1097/aln.0b013e31819b590a
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发表时间：
2009
期刊：
影响因子：
8.8
通讯作者：
HemmingsJr,HughC
中科院分区：
文献类型：
--
作者：
Perouansky,Misha;HemmingsJr,HughC
150 多年来，全身麻醉代表了医学药理学的典型胜利，为患者提供了无痛的遗忘，并为外科医生提供了一个安静的领域。但现在，对脆弱大脑的长期后遗症的担忧已经开始玷污全身麻醉剂迄今为止几乎一尘不染的形象。这些强效药物的治疗比率极低（如果不是因为它们的极端实用性，今天可能会妨碍监管部门的批准）是众所周知的；事实上，它们的专业使用和谨慎剂量构成了麻醉学实践的精髓。然而，引起科学家和公众关注的却是有关发育中和衰老大脑延迟和长期损害的报告。‡ Head 等人的复杂而及时的报告。在本期麻醉学 1 中，阐明了麻醉剂与哺乳动物大脑相互作用的复杂性和环境特异性。Head 等人。研究了异氟烷与神经元生长因子、脑源性神经营养因子 (BDNF) 2 和组织纤溶酶原激活剂 (tPA) 的相互作用，tPA 是一种丝氨酸蛋白酶，以其在纤维蛋白溶解中的血液学作用及其作为溶栓剂的治疗应用而闻名。 3 BDNF 依赖性信号传导先前已被证实与新生大鼠体内三重麻醉混合物（一氧化二氮、咪达唑仑、异氟烷）激活神经细胞凋亡有关。 4 海德等人。通过提供证据证明单独接触异氟烷会减少神经元释放 tPA，从而破坏 BDNF 信号传导的促进生存和促进死亡之间的微妙平衡，从而扩展了这些发现。这种效应被认为通过减少 pro-BDNF 的成熟过程，对发育中的啮齿动物大脑中异氟烷介导的神经毒性至关重要。
FOR more than 150 yr, general anesthetics have represented the quintessential triumph of medical pharmacology, providing painless oblivion for patients and a quiet field for surgeons. But now, concerns over long-term sequelae in the vulnerable brain have begun to tarnish the heretofore almost spotless image of general anesthetics. The extremely low therapeutic ratios of these powerful agents (which would likely preclude regulatory approval today if not for their extreme utility) are well known; indeed their expert use and careful dosing forms the essence of the practice of anesthesiology. However, it is the reports of delayed and long-term damage to the developing and the aged brain that have attracted attention and concern from both scientists and the public.‡ The sophisticated and timely report by Head et al. in this issue of ANESTHESIOLOGY 1 illuminates some the complexity and context-specificity of anesthetic interactions with the mammalian brain.Head et al. investigated the interactions of isoflurane with neuronal growth factor brain-derived neurotrophic factor (BDNF) 2 and tissue plasminogen activator (tPA), a serine protease better known for its hematologic role in fibrinolysis and its therapeutic application as a thrombolytic agent. 3 BDNF-dependent signaling had been implicated previously in the activation of neuroapoptosis by a triple anesthetic cocktail (nitrous oxide, midazolam, isoflurane) in neonatal rats in vivo. 4 Head et al. extend these findings by providing evidence that exposure to isoflurane alone reduces release of tPA from neurons and thereby upsets the delicate balance between survivalpromoting and death-promoting aspects of BDNF signaling. This effect is proposed to be critical to isofluranemediated neurotoxicity in the developing rodent brain by reducing the processing of pro-BDNF to mature