Brunssen Susan H, Morgan Daniel L, Parham Frederick M, Harry G Jean
Laboratory of Molecular Toxicology, NIEHS, 111 TW Alexander Drive, PO Box 12233, Research Triangle Park, NC 27709, USA.
Toxicology. 2003 Dec 15;194(1-2):51-63. doi: 10.1016/j.tox.2003.08.003.
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.
接触一氧化碳会产生与血液中碳氧血红蛋白（COHb）水平相关的神经行为效应。有人提出，当血液中碳氧血红蛋白水平达到约35%时，神经行为任务就会受到干扰。本研究检测了使成年雄性Fischer 344大鼠血液中碳氧血红蛋白水平达到30 - 40%的一氧化碳暴露对其毒性临床体征、在先前学会的回避程序中的表现以及神经元和神经胶质组织病理学的影响。在由2小时暴露于50 ppm一氧化碳产生的5%背景血液碳氧血红蛋白水平或经空调处理的对照背景下，对大鼠施加15分钟的高浓度暴露（4000 ppm）。从仅用于鼻吸入的容器中取出后，经空调处理的对照组和50 ppm一氧化碳暴露组在2分钟内出现轻度嗜睡和活动减少的迹象，而在4000 ppm一氧化碳暴露后，这些迹象持续3 - 4分钟。在双向穿梭箱主动回避任务中的表现显示，50 ppm一氧化碳组大鼠与经空调处理的对照组之间没有差异，而4000 ppm一氧化碳暴露组的回避和逃避反应显著减少。组织学检查显示，海马体或小脑中没有延迟性神经元死亡或星形胶质细胞反应性的证据；然而，在暴露于4000 ppm一氧化碳的动物中，这两个区域均出现了明显的反应性小胶质细胞局灶性染色。虽然单独的50 ppm一氧化碳（5%碳氧血红蛋白）不会干扰回避表现，但与经空调处理的对照组相比，小脑中的小胶质细胞染色显著增加。小胶质细胞的这种区域和局灶性反应表明，需要进一步研究这种细微的细胞变化及其与碳氧血红蛋白水平的关系。
