title: Electrical stimulation of the parabrachial nucleus induces reanimation from isoflurane general anesthesia.
abstract: Clinically, emergence from general anesthesia is viewed as a passive process where anesthetics are discontinued at the end of surgery and anesthesiologists wait for the drugs to wear off. The mechanisms involved in emergence are not well understood and there are currently no drugs that can actively reverse the state of general anesthesia. An emerging hypothesis states that brain regions that control arousal become active during emergence and are a key part of the return to wakefulness. In this study, we tested the hypothesis that electrical activation of the glutamatergic parabrachial nucleus (PBN) in the brainstem is sufficient to induce reanimation (active emergence) during continuous isoflurane general anesthesia. Using c-Fos immunohistochemistry as a marker of neural activity, we first show a selective increase in active neurons in the PBN during passive emergence from isoflurane anesthesia. We then electrically stimulated the PBN to assess whether it is sufficient to induce reanimation from isoflurane general anesthesia. Stimulation induced behavioral arousal and restoration of the righting reflex during continuous isoflurane general anesthesia. In contrast, stimulation of the nearby central inferior colliculus (CIC) did not restore the righting reflex. Spectral analysis of the electroencephalogram (EEG) revealed that stimulation produced a significant decrease in EEG delta power during PBN stimulation. The results are consistent with the hypothesis that the PBN provides critical arousal input during emergence from isoflurane anesthesia.
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, United States. Electronic address: fmuindi@mit.edu.
authors.forename: Fanuel
authors.initials: F
authors.lastname: Muindi
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kenny
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States.
authors.forename: Norman E
authors.initials: NE
authors.lastname: Taylor
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States.
authors.forename: Ken
authors.initials: K
authors.lastname: Solt
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, United States.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Wilson
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, United States; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United States; Harvard-Massachusetts Institute of Technology Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States.
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, United States. Electronic address: vandortc@mit.edu.
authors.forename: Christa J
authors.initials: CJ
authors.lastname: Van Dort
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D058256:Brain Waves / Q000187:drug effects* / Q000502:physiology; D002452:Cell Count; D004558:Electric Stimulation / Q000379:methods*; D004569:Electroencephalography; D005786:Gene Expression Regulation / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065823:Parabrachial Nucleus / Q000187:drug effects* / Q000502:physiology*; D011336:Probability; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D016760:Proto-Oncogene Proteins c-fos; D007530:Isoflurane