Carbon monoxide neurotoxicity: transient inhibition of avoidance response and delayed microglia reaction in the absence of neuronal death.
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.
Brunssen
Susan H
SH
Laboratory of Molecular Toxicology, NIEHS, 111 TW Alexander Drive, PO Box 12233, Research Triangle Park, NC 27709, USA.
Morgan
Daniel L
DL
Parham
Frederick M
FM
Harry
G Jean
GJ
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
D002248:Carbon Monoxide; D002263:Carboxyhemoglobin