Thom SR et al: Delayed neuropathology after carbon monoxide poisoning is immune-mediated. Proc Natl Acad Sci USA 101 : 13660-13665, 2004
The neuropathological sequelae of carbon monoxide (CO) poisoning cannot be explained by hypoxic stress alone. CO poisoning also causes adduct formation between myelin basic protein (MBP) and malonylaldehyde, a reactive product of lipid peroxidation, resulting in an immunological cascade. MBP loses its normal cationic characteristics, and antibody recognition of MBP is altered. Immunohistochemical evidence of degraded MBP occurs in brain over days, along with influx of macrophages and CD-4 lymphocytes. Lymphocytes from CO-poisoned rats subsequently exhibit an auto-reactive proliferative response to MBP, and there is a significant increase in the number of activated microglia in brain. Rats rendered immunologically tolerant to MBP before CO poisoning exhibit acute biochemical changes in MBP but no lymphocyte proliferative response or brain microglial activation. CO poisoning causes a decrement in learning that is not observed in immunologically tolerant rats. These results demonstrate that delayed CO-mediated neuropathology is linked to an adaptive immunological response to chemically modified MBP.
Thom SR et al. Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. Toxicology and applied pharmacology 213:152-159, 2006.
The goal of this investigation was to determine whether exposure to hyperbaric oxygen (HBO(2)) would ameliorate biochemical and functional brain abnormalities in an animal model of carbon monoxide (CO) poisoning. In this model, CO-mediated oxidative stress causes chemical alterations in myelin basic protein (MBP), which initiates an adaptive immunological response that leads to a functional deficit. CO-exposed rats do not show improvements in task performance in a radial maze. We found that HBO(2) given after CO poisoning will prevent this deficit, but not eliminate all of the CO-mediated biochemical alterations in MBP. MBP from HBO(2) treated CO-exposed rats is recognized normally by a battery of antibodies, but exhibits an abnormal charge pattern. Lymphocytes from HBO(2)-treated and control rats do not become activated when incubated with MBP, immunohistological evidence of microglial activation is not apparent, and functional deficits did not occur, unlike untreated CO-exposed rats. The results indicate that HBO(2) prevents immune-mediated delayed neurological dysfunction following CO poisoning.
Ide T and Yoshito K: Myelin basic protein in cerebrospinal fluid: a predictive marker of delayed encephalopathy from carbon monoxide poisoning. Am J Emerg Med 26: 908-912, 2008.
This study was designed to investigate whether myelin basic protein (MBP) in cerebrospinal fluid (CSF) can be a predictive marker of delayed encephalopathy from carbon monoxide (CO) poisoning. Five patients with CO poisoning were included in the study. The CSF was serially sampled to determine the MBP concentration. All patients were classified into group DE or group non-DE according to whether delayed encephalopathy developed or not. In all 3 patients in group DE, the MBP levels in the CSF were markedly elevated preceding the clinical manifestations of delayed encephalopathy. In both group non-DE patients, the MBP concentrations in the CSF were never elevated. Elevated MBP concentrations in the CSF may represent a predictive marker of delayed encephalopathy from CO poisoning, leading to a more appropriate triage of patients with CO poisoning.
阿部仁紀, 丹野善博, 石原哲也, 會田隆志, 関晴朗, 片山宗一, 山本悌司:ステロイドパルス療法が有効であった一酸化炭素中毒後の遅発性白質脳症の1例, 神経治療学 26: 625-631, 2009. (Medical onlineで閲覧可能)