Effects of Carbon Monoxide Poisoning on Nitric Oxide Synthase Containing Neurons in Rat Brain

J Korean Neurol Assoc > Volume 15(4); 1997 > Article

Journal of the Korean Neurological Association 1997;15(4): 719-727.

일산화탄소중독이 NO합성효소를 함유한 백서 신경세포에 미치는 영향

충북대학교 의과대학 신경과학교실

Effects of Carbon Monoxide Poisoning on Nitric Oxide Synthase Containing Neurons in Rat Brain

Seol-Heui Han, M.D.

Department of neurology, Chungbuk National University College of Medicine

Abstract

Acute carbon monoxide (CO) poisoning primarily affects the central nervous system(CNS), and survivors of severe CO poisoning often suffer permanent neuropsychiatric sequelae. The most widely recognized long-term sequelae of acute CO poisoning are neurobehavioral abnormalities varying from mild personality changes, difficulty in learning and behavioral problems, to irreversible dementia. The mechanisms of these processes are poorly understood although same investigators have suggested the involvement of CO-mediated brain cerebral mitochondrial energy metabolism. Since cellular injury by almost any mechanism has the potential to accelerate free radical reactions, it appears that reactive oxygen species (ROS) may have a critical role in CO-induced brain injury. There is evidence in rats that CO vulnerable brain regions show increased production of hydrogen peroxide and hydroxyl radical after acute poisoning. On the other hand, recent evidence suggests that the novel free radical neuromodulator, nitric oxide (NO), mediates NMDA receptor-linked excitotoxicity, and that neurons that contain NO synthase (NOS) are themselves spared from NMDA and NO toxic effects. NADPH-diaphorase neurons preferentially survive in the striatum in patients with Huntington's disease, Alzheimer's disease, and relatively spared in experimental models of brain damage due to ischemia or NMDA-mediated neurotoxins. In contrast to these findings, current experiment revealed that some of NOS neuons underwent degenerative changes several days after CO exposure. Moreover, oxidative stress itself could be a mediator of apoptosis much as programmed cell death associated with experimental focal cerebral ischemia in rats. Likewise apoptosis after CO poisoning might be a cause of cell death in addition to conventional necrotic cell death. Subsequent studies are needed to verify this conjecture, which eventually can elucidate the 'biphasic' clinical features of CO poisoning.