title: Inner ear lesion and the differential roles of hypoxia and hypercarbia in triggering active movements: Potential implication for the Sudden Infant Death Syndrome.
abstract: Infants that succumb to Sudden Infant Death Syndrome (SIDS) have been identified with inner ear dysfunction (IED) at birth and on autopsy. We previously investigated whether IED could play a mechanistic role in SIDS. We discovered that animals with IED displayed significant suppression of movement arousal to a hypoxic-hypercarbic gas mixture under light anesthesia. In the current study we investigated the role of each gas in triggering movements and the response to hypercarbia during natural sleep without anesthesia. Seventeen-day-old CD-1 mice received intra-tympanic gentamicin (IT-Gent) injections to precipitate IED. The movement response to hypercarbia, hypoxia and hypoxia-hypercarbia was compared to controls under light anesthesia. Hypercarbia did not stimulate vigorous movements in any animals under either sleep condition. Hypoxia triggered vigorous movements in controls (p<0.05) and a decreased response in IT-Gent animals under light anesthesia. This contrasted with combined hypoxia-hypercarbia, in which IT-Gent animals displaced significantly suppressed movements compared to controls (p<0.05). Our findings portray that a degree of intact inner ear function is necessary for instigating the movement response. Additionally, hypoxia is the trigger for the movement response while carbon dioxide (CO2) suppresses it. The finding that carbon dioxide did not stimulate movement during natural sleep is an important finding. This contrasts with other studies that have identified hypercarbia as an arousal stimulus with EEG. Further studies are warranted to evaluate the precise role of the inner ear in the movement response and potential association with SIDS. The early detection of IED in SIDS predisposed cases could be invaluable.
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, United States.
authors.forename: Sanja
authors.initials: S
authors.lastname: Ramirez
authors.affiliation: Department of Anesthesia, Seattle Children's Hospital, 4800 Sandpoint Way NE, Seattle, WA 98105, United States; Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, United States; Department of Anesthesia, University of Washington, Seattle, WA, United States.
authors.forename: Travis
authors.initials: T
authors.lastname: Allen
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, United States.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Villagracia
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, United States.
authors.forename: Yooree
authors.initials: Y
authors.lastname: Chae
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, United States; Department of Pediatrics, University of Washington, Seattle, WA, United States.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Ramirez
authors.affiliation: Department of Anesthesia, Seattle Children's Hospital, 4800 Sandpoint Way NE, Seattle, WA 98105, United States; Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, United States; Department of Anesthesia, University of Washington, Seattle, WA, United States. Electronic address: Daniel.rubens@seattlechildrens.org.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Rubens
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology; D007758:Ear, Inner / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005839:Gentamicins / Q000378:metabolism; D006801:Humans; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology*; D000860:Hypoxia / Q000378:metabolism*; D007223:Infant; D008297:Male; D051379:Mice; D009068:Movement / Q000502:physiology; D012890:Sleep / Q000502:physiology*; D013398:Sudden Infant Death
chemical_list: D005839:Gentamicins
keywords: SIDS; arousal; gentamicin; hypoxia-hypercarbia; inner-ear dysfunction; vestibular