Project/Area Number |
15390472
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Anesthesiology/Resuscitation studies
|
Research Institution | University of Fukui (2004-2005) 福井医科大学 (2003) |
Principal Investigator |
FUKUDA Satoru University of Fukui, Faculty of Medical Sciences, Professor, 医学部, 教授 (30116751)
|
Co-Investigator(Kenkyū-buntansha) |
SUZUKI Hisato University of Fukui, Faculty of Medical Sciences, lecturer, 医学部, 助手 (90235987)
YASUDA Yoshikazu University of Fukui, Faculty of Medical Sciences, Assistant Professor, 医学部附属病院, 講師 (50252002)
HIGUCHI Takashi University of Fukui, Faculty of Medical Sciences, Professor, 医学部, 教授 (70106326)
冨士原 秀善 福井大学, 医学部, 助教授 (20251803)
|
Project Period (FY) |
2003 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥10,300,000 (Direct Cost: ¥10,300,000)
|
Keywords | Orexin / Hypothalamus / Chorinergic arousal system / Basal forebrain / Isoflurane / Electroencephalogram / Acetylcholine / Glutamate / cholinergic arousal system / GABA / Pedunculopontine tegmentum nueleus / サポリン / コリン作動性神経系 / pedunculopontine tegmentum nucleus / 脳室内投与 / ヒスタミン / 麻酔 / イソフルレン |
Research Abstract |
Orexin has been reported to have the various actions of increases in feeding, maintenance of wakefulness, pain relief as well as activation of sympathetic nervous system. Among these actions of orexin, the maintenance of wakefulness induced by orexins might contribute to the emergence from anesthesia. In the brain, there are various arousal systems such as noradrenergic, cholinergic, histaminergic, serotonergic and dopaminergic systems. It has been reported that the cholinergic arousal system may contribute to the emergence from isoflurane, sevoflurane, propofol and neuroleptanestesia. Thus, we focused on the role of cholinergic system on the emergence from anesthesia in relation to orexinergic system. From our studies, we got the following results. 1) Intraventricular injection of orexin activated the electroencephalogram (EEG) under deep isoflurane anesthesia in the rat. 2) Microinjection of glutamate into the posterior hypothalamus induced EEG arousal through acting on the orexin ne
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urons. 3) The selective destruction of lateral hypothalamus with orexin-saporin decreased the minimum alveolar concentration of isoflurane. 4) Isoflurane dose-dependently increased the efflux of glutamate in the basal forebrain, not in the posterior hypothalamus and the cortex. Further, under isoflurane anesthesia, microinjection of AMPA, a glutamate receptor agonist, dose-dependently increased the efflux of acetylcholine (Ach) from the cortex, suggesting that the anesthetic level of isoflurane may be balanced between the inhibitory action of isoflurane and the excitatory action of glutamate induced by this agent. 5) Under isoflurane anesthesia, microinjection of orexins into the basal forebrain induced the increases in Ach efflux and activated EEG. In addition, the electrical stimulation of the pedunculopontine tegmentum, the origin of cholinergic ascending pathways, increased the cortical Ach efflux and the EEG arousal under isoflurane anesthesia. These actions were antagonized by SB334867, a selective orexin-1 receptor antagonist. From all the findings, we concluded that orexinergic system may contribute to the emergence from anesthesia through cholinergic arousal system. Less
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