Liver-brain proinflammatory signalling in acute liver failure: Role in the pathogenesis of hepatic encephalopathy and brain edema
Liver-brain proinflammatory signalling in acute liver failure: Role in the pathogenesis of hepatic encephalopathy and brain edema
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DOI：
10.1007/s11011-012-9361-3
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发表时间：
2013-06-01
影响因子：
3.6
通讯作者：
Butterworth, Roger F.
中科院分区：
文献类型：
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作者：
Bemeur, Chantal;Butterworth, Roger F.
在急性肝衰竭（ALF）中，以小胶质细胞激活和促炎细胞因子脑生成增加为特征的强烈神经炎症反应是常见的。目前提出的解释ALF神经炎症反应的机制包括系统来源的促炎细胞因子的直接作用以及脑乳酸积累对活化小胶质细胞释放促炎细胞因子的影响。细胞培养研究揭示了氨和促炎细胞因子对谷氨酸稳态和氧化/亚硝化应激相关蛋白表达的积极协同作用。促炎细胞因子具有改变血脑屏障（BBB）完整性的能力，初步研究表明，ALF感染可导致血脑屏障破裂和血管源性脑水肿。目前正在研究的有效预防ALF脑病和脑水肿的治疗方法，旨在减少ALF的神经炎症，包括轻度低温、白蛋白透析系统、n -乙酰半胱氨酸和抗生素米诺环素，它们具有有效的抗炎作用，不同于其抗微生物特性。
A robust neuroinflammatory response characterized by microglial activation and increased brain production of pro-inflammatory cytokines is common in acute liver failure (ALF). Mechanisms proposed to explain the neuroinflammatory response in ALF include direct effects of systemically-derived proinflammatory cytokines and the effects of brain lactate accumulation on pro-inflammatory cytokine release from activated microglia. Cell culture studies reveal a positive synergistic effect of ammonia and pro-inflammatory cytokines on the expression of proteins involved in glutamate homeostasis and in oxidative/nitrosative stress. Proinflammatory cytokines have the capacity to alter blood-brain barrier (BBB) integrity and preliminary studies suggest that the presence of infection in ALF results in rupture of the BBB and vasogenic brain edema. Treatments currently under investigation that are effective in prevention of encephalopathy and brain edema in ALF which are aimed at reduction of neuroinflammation in ALF include mild hypothermia, albumin dialysis systems, N-acetyl cysteine and the antibiotic minocycline with potent anti-inflammatory actions that are distinct from its anti-microbial properties.