An essential role for orexins in emergence from general anesthesia.

An essential role for orexins in emergence from general anesthesia. Research Abstract Details 

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An essential role for orexins in emergence from general anesthesia. Abstract Text:

Max B Kelz,Yi Sun,Jingqiu Chen,Qing Cheng Meng,Jason T Moore,Sigrid C Veasey,Shelley Dixon,Marcus Thornton,Hiromasa Funato,Masashi Yanagisawa,

The neural mechanisms through which the state of anesthesia arises and dissipates remain unknown. One common belief is that emergence from anesthesia is the inverse process of induction, brought about by elimination of anesthetic drugs from their CNS site(s) of action. Anesthetic-induced unconsciousness may result from specific interactions of anesthetics with the neural circuits regulating sleep and wakefulness. Orexinergic agonists and antagonists have the potential to alter the stability of the anesthetized state. In this report, we refine the role of the endogenous orexin system in impacting emergence from, but not entry into the anesthetized state, and in doing so, we distinguish mechanisms of induction from those of emergence. We demonstrate that isoflurane and sevoflurane, two commonly used general anesthetics, inhibit c-Fos expression in orexinergic but not adjacent melanin-concentrating hormone (MCH) neurons; suggesting that wake-active orexinergic neurons are inhibited by these anesthetics. Genetic ablation of orexinergic neurons, which causes acquired murine narcolepsy, delays emergence from anesthesia, without changing anesthetic induction. Pharmacologic studies with a selective orexin-1 receptor antagonist confirm a specific orexin effect on anesthetic emergence without an associated change in induction. We conclude that there are important differences in the neural substrates mediating induction and emergence. These findings support the concept that emergence depends, in part, on recruitment and stabilization of wake-active regions of brain.

An essential role for orexins in emergence from general anesthesia. Publishing Authors By Initials

MB Kelz,Y Sun,J Chen,Q Cheng Meng,JT Moore,SC Veasey,S Dixon,M Thornton,H Funato,M Yanagisawa,

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An essential role for orexins in emergence from general anesthesia. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 105

Page Numbers: 1309-14

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 1091-6490

DAY: 14

MONTH: 01

YEAR: 2008

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for An essential role for orexins in emergence from general anesthesia.

AFFILIATION: Department of Anesthesiology and Critical Care, Mahoney Institute for Neurological Sciences, Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, Philadelphia, PA 19104, USA. kelzma@uphs.upenn.edu

Country: United States

AGENCY: United States NIGMS

GRANT: K08-GM077357

ACRONYM: GM

MEDLINETA: Proc Natl Acad Sci U S A

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