Stud for the mechanism of aging and anesthesia-related sleep disorder and its treatment.

研究衰老和麻醉相关睡眠障碍的机制及其治疗。

• 批准号: 21390430
• 负责人: HIROTA Kazuyoshi
• 金额: $ 8.99万
• 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: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390430/
• 关键词: 睡眠障害; 加齢; ラット; 全身麻酔; 神経生理活性物質; 鎮静; オピオイド

In this study, although age-related sleep disorder was confirmed in rats, we could not recognize a difference with the length of each sleep stage between adult and aged rats. Then, we also studied post-anesthesia sleep disorder and determine the difference of sleep disorder after both type(GABA_A receptor activation[GABA type] or NMDA receptor inhibition[NMDA-type]) of anesthetic agent-induced anesthesia. We found that REM sleep significantly increased a few days after ketamine (NMDA-type) anesthesia while no significant differences in each sleep stage between pre- and post propofol anesthesia were observed. Ketamine-induced post-anesthesia sleep disorder is similar to post-surgical sleep disorder that is considered as a main factor of postoperative respiratory and cardiovascular complications. Thus, ketamine-induced post-anesthesia sleep disorder may be used as a post-surgical sleep disorder model. In addition, this post-anesthesia sleep disorder was almost fully antagonized by icv orexin A or neuropeptide S. If prexin A or neuropeptide S analogues that are un-metabolized in the plasma and penetrated into blood brain barrier after their systemic administration will be developed, we may be able to treat post-surgical sleep disorder.

在这项研究中，尽管在大鼠中证实了与年龄相关的睡眠障碍，但我们无法认识到成年大鼠和年龄大鼠之间每个睡眠阶段的长度有所不同。然后，我们还研究了麻醉剂诱导的麻醉性麻醉剂的麻醉性抑制作用（GABA_A受体激活[GABA类型]或NMDA受体抑制[NMDA-type]）类型后睡眠障碍的差异。我们发现，在氯胺酮（NMDA型）麻醉后几天，REM睡眠显着增加，而观察到丙泊酚前麻醉前后每个睡眠阶段没有显着差异。氯胺酮引起的麻醉后睡眠障碍类似于手术后睡眠障碍，该睡眠障碍被认为是术后呼吸道和心血管并发症的主要因素。因此，氯胺酮引起的麻醉后睡眠障碍可以用作手术后睡眠障碍模型。此外，这种麻醉后的睡眠障碍几乎被ICV Orexin A或神经肽S完全拮抗。

项目成果

Orexin A attenuates sleep-disturbance following ketamine Anesthesia

食欲素 A 可减轻氯胺酮麻醉后的睡眠障碍

• 发表时间: 2009
• 作者: Takeda;Y.;Takada;Y.;Omote;K.;Matsuo;K.;Kushikata T
• 通讯作者: Kushikata T

Nitrous oxide and xenon increase noradrenaline release in the cerebral cortex in vivo and in vitro

一氧化二氮和氙增加体内和体外大脑皮层去甲肾上腺素的释放

• DOI: 10.1016/j.neulet.2009.11.074
• 发表时间: 2010
• 期刊: Neurosci Lett
• 影响因子: 2.5
• 作者: Yoshida H;Kushikata T;Tose R;Kudo M;Kudo T;Hirota K
• 通讯作者: Hirota K

The role of orexin in regulating general anesthesia

食欲素在调节全身麻醉中的作用

• 发表时间: 2010
• 作者: 伊東久勝;池上大悟;山崎光章;成田年;Yoshida H
• 通讯作者: Yoshida H

I Ketamine affects brain orexin A contents in rats.

I 氯胺酮影响大鼠大脑中食欲素 A 的含量。

• 发表时间: 2010
• 作者: Oishi M;Moriya K;Saito C;Kudo M;Kushikata T;Hirota K.
• 通讯作者: Hirota K.

Plasma orexin A increases at emergence trom sevotlurane-tentanyl anesthesia in patients undergoing ophthalmologic surgery.

接受眼科手术的患者在七氟烷-丁太尼麻醉苏醒后血浆食欲素 A 增加。

• 发表时间: 2010
• 期刊: Neurosci Lett
• 影响因子: 2.5
• 作者: Kushikata T;Yoshida H;Kudo M;Kudo T_ Hirota K.
• 通讯作者: Kudo T_ Hirota K.