title: Hyperoxia, reactive oxygen species, and hyperventilation: oxygen sensitivity of brain stem neurons.
abstract: Hyperoxia is a popular model of oxidative stress. However, hyperoxic gas mixtures are routinely used for chemical denervation of peripheral O2 receptors in in vivo studies of respiratory control. The underlying assumption whenever using hyperoxia is that there are no direct effects of molecular O2 and reactive O2 species (ROS) on brain stem function. In addition, control superfusates used routinely for in vitro studies of neurons in brain slices are, in fact, hyperoxic. Again, the assumption is that there are no direct effects of O2 and ROS on neuronal activity. Research contradicts this assumption by demonstrating that O2 has central effects on the brain stem respiratory centers and several effects on neurons in respiratory control areas; these need to be considered whenever hyperoxia is used. This mini-review summarizes the long-recognized, but seldom acknowledged, paradox of respiratory control known as hyperoxic hyperventilation. Several proposed mechanisms are discussed, including the recent hypothesis that hyperoxic hyperventilation is initiated by increased production of ROS during hyperoxia, which directly stimulates central CO2 chemoreceptors in the solitary complex. Hyperoxic hyperventilation may provide clues into the fundamental role of redox signaling and ROS in central control of breathing; moreover, oxidative stress may play a role in respiratory control dysfunction. The practical implications of brain stem O2 and ROS sensitivity are also considered relative to the present uses of hyperoxia in respiratory control research in humans, animals, and brain stem tissues. Recommendations for future research are also proposed.
authors.affiliation: Department of Anatomy and Physiology, Wright State University School of Medicine, College of Science and Mathematics, Dayton, Ohio 45435, USA. jay.dean@wright.edu
authors.forename: Jay B
authors.initials: JB
authors.lastname: Dean
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Mulkey
authors.forename: Richard A
authors.initials: RA
authors.lastname: Henderson
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Potter
authors.forename: Robert W
authors.initials: RW
authors.lastname: Putnam
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism / Q000503:physiopathology*; D006985:Hyperventilation / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D010100:Oxygen