Involvement of Tuberomamillary Histaminergic Neurons in Isoflurane Anesthesia
Involvement of Tuberomamillary Histaminergic Neurons in Isoflurane Anesthesia
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DOI：
10.1097/aln.0b013e3182207655
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发表时间：
2011-07-01
期刊：
影响因子：
8.8
通讯作者：
Leung, L. Stan
中科院分区：
文献类型：
--
作者：
Luo, Tao;Leung, L. Stan
背景：脑组胺能系统在唤醒的维持中起着关键作用。以前的研究表明，组胺能神经传递可能是全身麻醉作用的潜在介体。然而，组胺能结节乳头核(TMN)是否一定参与了全身麻醉药的镇静/催眠作用尚不清楚。方法：雄性Long Evans大鼠在实验前2周接受TMN增食欲素-皂苷/假损伤或侧脑室插管。用翻正反射丧失的行为终点来评估异氟醚、异丙酚、戊巴比妥和氯胺酮对动物的催眠作用。用免疫组织化学方法检测TMN中腺苷脱氨酶的表达。结果：与假损伤大鼠相比，双侧TMN增食欲素-皂苷损伤组大鼠的组胺能细胞平均损失72%。损毁TMN增食欲素-皂苷或侧脑室注射H1受体拮抗剂曲普利定可降低翻正反射值丧失的50%有效浓度，延长异氟醚苏醒时间。但损毁TMN食欲素-皂苷对异丙酚、戊巴比妥和氯胺酮的麻醉敏感性无显著影响。结论：TMN组胺能神经元在异氟醚麻醉的调节中起作用，异氟醚催眠的神经回路可能不同于γ-氨基丁酸介导的麻醉剂和氯胺酮。
Background: The brain histaminergic system plays a critical role in maintenance of arousal. Previous studies suggest that histaminergic neurotransmission might be a potential mediator of general anesthetic actions. However, it is not clear whether histaminergic tuberomamillary nucleus (TMN) is necessarily involved in the sedative/hypnotic effects of general anesthetics.Methods: Male Long Evans rats underwent either TMN orexin-saporin/sham lesion or implantation of intracerebroventricular cannula 2 weeks before the experiment. The behavioral endpoint of loss of righting reflex was used to assess the hypnotic property of isoflurane, propofol, pentobarbital, and ketamine in animals. Histaminergic cell loss was assessed by adenosine deaminase expression in the TMN using immunohistochemistry.Results: Rats with bilateral TMN orexin-saporin lesion induced an average 72% loss of histaminergic cells compared with sham-lesion rats. TMN orexin-saporin lesion or intracerebroventricular administration of triprolidine (an H1 receptor antagonist) decreased the 50% effective concentration for loss of righting reflex value and prolonged emergence time to isoflurane anesthesia. However, TMN orexin-saporin lesion had no significant effect on the anesthetic sensitivity to propofol, pentobarbital, and ketamine.Conclusions: These findings suggest a role of the TMN histaminergic neurons in modulating isoflurane anesthesia and that the neural circuits for isoflurane-induced hypnosis may differ from those of gamma-aminobutyric acid-mediated anesthetics and ketamine.