The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
An essential role for orexins in emergence from general anesthesia
Open accessAbstract
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.
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“using c-Fos as a proxy for antecedent activity, neurons within many of these nuclei have been identified to be inhibited during general anesthesia [98, 100, 101, 114].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [114]
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Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., Williams, S. C., Richardson, J. A., Kozlowski, G. P., Wilson, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80949-6 · Cited by 5,501
Self-citationNeurons containing hypocretin (orexin) project to multiple neuronal systems
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Narcolepsy in orexin Knockout Mice
Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, J. A., Williams, S. C., Xiong, Y., Kisanuki, Y., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)81973-x · Cited by 3,095
Self-citationHypothalamic regulation of sleep and circadian rhythms
Saper, C. B., Scammell, T. E., & Lu, J. (2005) · Nature · doi:10.1038/nature04284 · Cited by 2,804
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Genetic Ablation of Orexin Neurons in Mice Results in Narcolepsy, Hypophagia, and Obesity
Hara, J., Beuckmann, C. T., Nambu, T., Willie, J. T., Chemelli, R. M., Sinton, C. M., Sugiyama, F., Yagami, K.-I., Goto, K., Yanagisawa, M., et al. (2001) · Neuron · doi:10.1016/s0896-6273(01)00293-8 · Cited by 1,401
Self-citationA role for lateral hypothalamic orexin neurons in reward seeking
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Mechanisms of Actions of Inhaled Anesthetics
Campagna, J. A., Miller, K. W., & Forman, S. A. (2003) · New England Journal of Medicine · doi:10.1056/nejmra021261 · Cited by 805
Fos Expression in Orexin Neurons Varies with Behavioral State
Estabrooke, I. V., McCarthy, M. T., Ko, E., Chou, T. C., Chemelli, R. M., Yanagisawa, M., Saper, C. B., & Scammell, T. E. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01656.2001 · Cited by 654
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General Anesthesia, Sleep, and Coma
Brown, E. N., Lydic, R., & Schiff, N. D. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0808281 · Cited by 1,413
General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal
Franks, N. P. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2372 · Cited by 1,295
Boveroux, P., Vanhaudenhuyse, A., Bruno, M.-A., Noirhomme, Q., Lauwick, S., Luxen, A., Degueldre, C., Plenevaux, A., Schnakers, C., Phillips, C., et al. (2010) · Anesthesiology · doi:10.1097/aln.0b013e3181f697f5 · Cited by 630
Unresponsiveness ≠ unconsciousness
Sanders, R. D., Tononi, G., Laureys, S., Sleigh, J. W., & Warner, D. S. (2012) · Anesthesiology · doi:10.1097/aln.0b013e318249d0a7 · Cited by 474
Awareness and recall during general anesthesia
Chung, H. S. (2014) · Korean Journal of Anesthesiology · doi:10.4097/kjae.2014.66.5.339 · Cited by 301
Metadata
- Authors
- Kelz, M. B., Sun, Y., Chen, J., Cheng Meng, Q., Moore, J. T., Veasey, S. C., Dixon, S., Thornton, M., Funato, H., & Yanagisawa, M.
- Affiliations
- University of Pennsylvania (US)
- *Department of Anesthesiology and Critical Care,
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-01-29
- Volume
- 105
- Issue
- 4
- Pages
- 1309-1314
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2234134
- OpenAlex
- W2135826809
- Cited by
- 341
- References
- 36
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 21 · 2023: 17 · 2022: 14 · 2021: 30 · 2020: 25 · 2019: 18 · 2018: 19 · 2017: 12 · 2016: 13 · 2015: 14 · 2014: 22 · 2013: 11 · 2012: 19
- FWCI
- 13.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation for Anesthesia Education and Research
- University of Pennsylvania
- National Institutes of Health
- National Institute of General Medical Sciences (K08GM077357)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- orexin, emergence from anesthesia, general anesthesia, anesthesia induction, isoflurane, sevoflurane, Fos expression, orexinergic neurons, melanin-concentrating hormone neurons, orexin-1 receptor antagonist, sleep-wake regulation, loss of consciousness
- MeSH terms
- Orexins, Sevoflurane, Anesthesia, General, Animals, Female, Isoflurane, Male, Methyl Ethers, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Neuropeptides, Signal Transduction, Proto-Oncogene Proteins c-fos, Anesthetics, Inhalation, Protein Transport, Intracellular Signaling Peptides and Proteins, Mice
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