Mechanism of delayed encephalopathy after acute carbon monoxide poisoning.
Mechanism of delayed encephalopathy after acute carbon monoxide poisoning.
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DOI：
10.4103/1673-5374.284995
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发表时间：
2020-12
影响因子：
6.1
通讯作者：
Yang AL
中科院分区：
文献类型：
--
作者：
Huang YQ;Peng ZR;Huang FL;Yang AL
关于急性一氧化碳中毒后迟发性脑病（DEACMP）的机制存在许多假说，包括炎症和免疫介导的损伤假说以及细胞凋亡和直接神经元毒性假说;然而，现有的假说没有为DEACMP中观察到的复杂临床过程提供令人满意的解释。富含亮氨酸重复序列和免疫球蛋白样结构域蛋白-1（LINGO-1）激活Ras同源基因家族成员A（RhoA）/Rho相关卷曲螺旋蛋白激酶2（ROCK 2）信号通路，其负性调节少突胶质细胞髓鞘形成、轴突生长和神经元存活，引起髓鞘损伤并参与与许多中枢神经系统疾病相关的病理生理过程。然而，LINGO-1是否参与DEACMP仍不清楚。通过使大鼠吸入1000 ppm一氧化碳气体40分钟，然后再吸入3000 ppm一氧化碳气体20分钟，在大鼠中建立DEACMP模型。结果显示，与对照组相比，DEACMP组大鼠水迷宫潜伏期明显延长，脑组织LINGO-1、RhoA和ROCK 2蛋白和mRNA表达水平明显升高。与正常大鼠相比，DEACMP大鼠海马神经元损伤明显增加，外侧膝状体髓鞘损伤明显增加。从DEACMP后第1天到第21天，腹腔注射可抑制LINGO-1表达的视黄酸（10 mg/kg）能够改善DEACMP模型中观察到的上述变化。因此，LINGO-1的过表达似乎在一氧化碳中毒后增加，激活RhoA/ROCK 2信号通路，这可能是DEACMP的重要病理生理机制。本研究于2016年12月26日经中南医院湘雅医院医学伦理委员会审查通过（批件号：201612684）。
Many hypotheses exist regarding the mechanism underlying delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), including the inflammation and immune-mediated damage hypothesis and the cellular apoptosis and direct neuronal toxicity hypothesis; however, no existing hypothesis provides a satisfactory explanation for the complex clinical processes observed in DEACMP. Leucine-rich repeat and immunoglobulin-like domain-containing protein-1 (LINGO-1) activates the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathway, which negatively regulates oligodendrocyte myelination, axonal growth, and neuronal survival, causing myelin damage and participating in the pathophysiological processes associated with many central nervous system diseases. However, whether LINGO-1 is involved in DEACMP remains unclear. A DEACMP model was established in rats by allowing them to inhale 1000 ppm carbon monoxide gas for 40 minutes, followed by 3000 ppm carbon monoxide gas for an additional 20 minutes. The results showed that compared with control rats, DEACMP rats showed significantly increased water maze latency and increased protein and mRNA expression levels of LINGO-1, RhoA, and ROCK2 in the brain. Compared with normal rats, significant increases in injured neurons in the hippocampus and myelin sheath damage in the lateral geniculate body were observed in DEACMP rats. From days 1 to 21 after DEACMP, the intraperitoneal injection of retinoic acid (10 mg/kg), which can inhibit LINGO-1 expression, was able to improve the above changes observed in the DEACMP model. Therefore, the overexpression of LINGO-1 appeared to increase following carbon monoxide poisoning, activating the RhoA/ROCK2 signaling pathway, which may be an important pathophysiological mechanism underlying DEACMP. This study was reviewed and approved by the Medical Ethics Committee of Xiangya Hospital of Central South Hospital (approval No. 201612684) on December 26, 2016.
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影响因子：
4.6
作者：
Almutiri S;Berry M;Logan A;Ahmed Z
通讯作者：
Ahmed Z
DOI：
10.3233/jad-130236
发表时间：
2014
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
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影响因子：
3.5
作者：
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影响因子：
5.7
作者：
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