Carbon monoxide poisoning-induced delayed encephalopathy accompanies decreased microglial cell numbers: Distinctive pathophysiological features from hypoxemia-induced brain damage
Carbon monoxide poisoning-induced delayed encephalopathy accompanies decreased microglial cell numbers: Distinctive pathophysiological features from hypoxemia-induced brain damage
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DOI：
10.1016/j.brainres.2018.12.027
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发表时间：
2019-05-01
期刊：
影响因子：
2.9
通讯作者：
Yorozuya, Toshihiro
中科院分区：
文献类型：
--
作者：
Sekiya, Keisuke;Nishihara, Tasuku;Yorozuya, Toshihiro
一氧化碳（CO）不仅引起急性致命中毒，还可能引起一种称为迟发性脑病（DE）的迟发性神经系统综合征，这种情况偶尔会在接触后几天到几周后发生。然而，DE的机制尚未完全阐明。本研究旨在阐明co诱导DE的病理生理机制及其与低氧性缺氧的区别。大鼠随机分为三组；空气组、CO组（暴露于CO）和低O-2组（暴露于低浓度的O-2）。仅在CO组观察到记忆功能损伤。收集海马组织，分析co诱导的变化和小胶质细胞反应。仅CO组出现脱髓鞘，且脱髓鞘比低O-2组更严重，持续时间更长。流式细胞术观察到CO组小胶质细胞数量减少，免疫组化观察到小胶质细胞分支分离。相反，低氧组小胶质细胞分支缩短，体体增大。此外，小胶质细胞表达的编码几种神经营养因子的mrna在CO组中减少，而在低O-2组中增加。因此，co诱导的DE表现出与单纯缺氧损伤不同的病理特征：脱髓鞘延长，伴随小胶质细胞显著减少。小胶质细胞神经营养因子表达降低可能是co诱导DE的原因之一。
Carbon monoxide (CO) causes not only acute fatal poisoning but also may cause a delayed neurologic syndrome called delayed encephalopathy (DE), which occasionally occurs after an interval of several days to several weeks post-exposure. However, the mechanisms of DE have not been fully elucidated. This study aimed to clarify the pathophysiology of CO-induced DE and its distinctive features compared with hypoxemic hypoxia. Rats were randomly assigned to three groups; the air group, the CO group (exposed to CO), and the low O-2 group (exposed to low concentration of O-2). Impairment of memory function was observed only in the CO group. The hippocampus tissues were collected and analyzed for assessment of CO-induced changes and microglial reaction. Demyelination was observed only in the CO group and it was more severe and persisted longer than that observed in the low O-2 group. Moreover, in the CO group, decreased in microglial cell numbers were observed using flow cytometry, and microglia with detached branches were observed were observed using immunohistochemistry. Conversely, microglial cells with shortened branches and enlarged somata were observed in the low O-2 group. Furthermore, mRNAs encoding several neurotrophic factors expressed by microglia were decreased in the CO group but were increased in the low O-2 group. Thus, CO-induced DE displayed distinctive pathological features from those of simple hypoxic insults: prolonged demyelination accompanying a significant decrease in microglial cells. Decreased neurotrophic factor expression by microglial cells may be one of the causes of CO-induced DE.