Unitary mechanism of general anesthesia using brain noradrenergic neuronal network.

使用脑去甲肾上腺素能神经元网络进行全身麻醉的单一机制。

基本信息

批准号：
14370480
负责人：
HIROTA Kazuyoshi
金额：
$ 8.96万
依托单位：
Hirosaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

In Vitro1.Effects of orexin(OX) on neurotransmitter releases from the cerebral cortex.Both OXA and B concentration-dependently increased only norepinephrine(NE) release but did not other neurotransmitters such as dopamine, glutamate, 5HT and histamine. Therefore, OX may selectively increase NE release from rat cerebral cortex.2.Effects of OX_1 antagonist on OXA and B-evoked NE 放出 release.As SB334867,an OX1 antagonist, almost fully inhibited OXs-evoked NE release, the release may be mediated via OX_1 receptors.3.Effects of anesthetics on OX-evoked NE release.1)GABA-type anesthetics : Clinically relevant concentrations of anesthetic barbiturates significantly inhibited OX-evoked NE release. However, inhibitory effects of thiopental on the OX-evoked release was not reversed by bicuculline, a GABA_A receptor antagonist. In addition, muscimol, a GABA_A receptor agonist, did not inhibit the OX-evoked release. Therefore, anesthetic barbiturates may inhibit OXergic neurons not via GABA_A receptors.3)NMDA-type anesthetics : Ketamine significantly inhibited OXA-evoked NE release hi its clinical range. In addition, MK801,a NMDA receptor antagonist, also inhibited the release. Therefore, inhibitory effects of ketamine may be mediated via NMDA receptors.In Vivo1.Effects of icv OX on cerebrocortical NE release.Iev OXA dose-dependently increased cerebrocortical NE release, which was confirmed with microdialysis method. The degree of increases in NE release by icv OXA was similar to that of OXA-evoked NE release from in vitro cerebrocortical slices.2.Influence of icv OX on anesthesia time.1)GABA-type anesthetics : Icv OXs significantly decreased barbiturate-anesthesia time. In contrast, OX1 antagonist increased the time.2)NMDA-type anesthetics : Icv OXA significantly inhibited ketamine-anesthesia time. This inhibition was antagonized by OX1 antagonist.

体外1. Orexin（ox）对神经递质的影响从脑皮质中释放出来。OXA和B浓度依赖性地增加了去甲肾上腺素（NE）的释放，但没有其他神经递质的释放，但没有其他神经递质（例如多巴胺，多巴胺，谷氨酸，5HT和Histamine）。因此，OX可能会选择性地增加大鼠脑皮质的NE释放。2。OX_1拮抗剂对OXA和B诱发的NE释放的效果。AS SB334867（AS SB334867），一种OX1拮抗剂，几乎完全抑制OXS诱发的NE释放，该释放可以通过OX_1受体介导。麻醉药：麻醉巴比妥类药物的临床相关浓度显着抑制了牛诱发的NE释放。然而，硫代诱发的释放的抑制作用并未被gaba_a受体拮抗剂Bicuculline逆转。此外，GABA_A受体激动剂Muscimol并未抑制OX诱发的释放。因此，麻醉巴比妥类药物可能不会通过GABA_A受体抑制氧气神经元。3）NMDA型麻醉药：氯胺酮显着抑制了OXA诱发的NE释放的临床范围。此外，NMDA受体拮抗剂MK801也抑制了释放。因此，氯胺酮的抑制作用可以通过NMDA接收器介导。在Vivo1。iCV ox对脑皮层NE释放的影响。ExA剂量依赖性地依赖性地增加了脑皮质NE释放，并用微量学层次的方法证实。 ICV OXA释放NE释放的程度与从体外脑皮层切片中释放的NE释放相似。2。ICV OX在麻醉时间内的发作性。1）GABA型麻醉药：ICV OX可显着改善了改善的Bariturate bitbiturate-bitaretrate-nanecthesiia时间。相反，OX1拮抗剂增加了时间。2）NMDA型麻醉药：ICV OXA显着抑制氯胺酮 - 麻醉时间。这种抑制作用被OX1拮抗剂拮抗。