title: Carbon monoxide neurotoxicity: transient inhibition of avoidance response and delayed microglia reaction in the absence of neuronal death.
abstract: Carbon monoxide exposure produces neurobehavioral effects associated with the level of carboxyhemoglobin (COHb) in the blood. A threshold has been proposed of approximately 35% COHb for the manifestation of disruption in neurobehavioral tasks. The effects of CO exposure producing 30-40% carboxyhemoglobin (COHb) levels in young adult male Fischer 344 rats were examined with regard to clinical signs of toxicity, performance on a previously learned avoidance procedure, and neuronal and glia histopathology. High levels of exposure (4000 ppm) for 15 min were imposed on either a background blood COHb level of 5% produced by a 2 h exposure to 50 ppm CO or a control background from conditioned-air exposure. Upon removal from the nose-only inhalation holder, signs of mild lethargy and decreased activity were evident for 2 min for conditioned-air controls and 50 ppm CO exposure groups and 3-4 min following 4000 ppm CO. Performance on a two-way shuttle box active avoidance task showed no differences between 50 ppm CO rats and conditioned-air controls while the 4000 ppm CO exposed groups showed a significant decrease in avoidance and escape responses. Histological examination showed no evidence of delayed neuronal death or astrocyte reactivity in the hippocampus or cerebellum; however, a distinct focal staining of reactive microglia in both regions was evident in animals exposed to 4000 ppm CO. While 50 ppm CO (5% COHb) alone produced no disruption in avoidance performance, microglia staining in the cerebellum was significantly increased over conditioned-air controls. This regional and focal response of microglia suggests the need for further study regarding such subtle cellular changes and their relationship with COHb levels.
authors.affiliation: Laboratory of Molecular Toxicology, NIEHS, 111 TW Alexander Drive, PO Box 12233, Research Triangle Park, NC 27709, USA.
authors.forename: Susan H
authors.initials: SH
authors.lastname: Brunssen
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Morgan
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Parham
authors.forename: G Jean
authors.initials: GJ
authors.lastname: Harry
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D002248:Carbon Monoxide / Q000633:toxicity*; D002263:Carboxyhemoglobin / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D002248:Carbon Monoxide; D002263:Carboxyhemoglobin