Peripheral administration of fetuin-A attenuates early cerebral ischemic injury in rats.
Peripheral administration of fetuin-A attenuates early cerebral ischemic injury in rats.
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DOI：
10.1038/jcbfm.2009.247
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发表时间：
2010-03
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脑缺血引起的炎症反应由中枢（例如，神经元和小胶质细胞）和浸润性外周免疫细胞（例如，巨噬细胞/单核细胞），并有助于组织损伤的演变。一种普遍存在的分子，精胺，从受损细胞释放，并反调节各种促炎细胞因子的释放。然而，精胺介导的抗炎活性依赖于胎球蛋白-A的可用性，胎球蛋白-A是一种肝源性负急性期蛋白。使用局灶性脑缺血的动物模型（即，永久性大脑中动脉闭塞（MCAo）后，我们发现缺血脑组织中胎球蛋白-A的水平以时间依赖性方式升高，在MCAo后2-6小时之间开始，在24-48小时左右达到峰值，并在72小时回到基线。当外周给药时，外源性胎球蛋白-A通过血脑屏障进入缺血性脑组织，并在MCAo后24小时剂量依赖性地减少脑梗死体积。同时，胎球蛋白-A有效地减弱：i）缺血诱导的HMGB 1从缺血核心的消耗; ii）中枢-（例如，小胶质细胞）和外周来源的免疫细胞（例如，巨噬细胞/单核细胞）;和iii）缺血性脑组织中的TNF产生。总之，这些实验数据表明，胎球蛋白-A是保护对早期脑缺血性损伤，部分通过减弱脑炎症反应。
Cerebral ischemia-elicited inflammatory responses are driven by inflammatory mediators produced both by central (e.g., neurons and microglia) and infiltrating peripheral immune cells (e.g., macrophage/monocyte), and contribute to the evolution of tissue injury. A ubiquitous molecule, spermine, is released from injured cells, and counter-regulates release of various proinflammatory cytokines. However, the spermine-mediated anti-inflammatory activities are dependent on the availability of fetuin-A, a liver-derived negative acute-phase protein. Using an animal model of focal cerebral ischemia (i.e., permanent middle cerebral artery occlusion, MCAo), we found that levels of fetuin-A in the ischemic brain tissue were elevated in a time-dependent manner, starting between 2–6 h, peaking around 24–48 h, and returning towards base-line at 72 h post MCAo. When given peripherally, exogenous fetuin-A gained entry across the blood-brain barrier into the ischemic brain tissue, and dose-dependently reduced brain infarct volume at 24 h post MCAo. Meanwhile, fetuin-A effectively attenuated: i) ischemia-induced HMGB1 depletion from the ischemic core; ii) activation of centrally- (e.g., microglia) and peripherally-derived immune cells (e.g., macrophage/monocytes); and iii) TNF production in ischemic brain tissue. Taken together, these experimental data suggest that fetuin-A is protective against early cerebral ischemic injury partly by attenuating the brain inflammatory response.
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影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
4.4
作者：
Li, Wei;Li, Jianhua;Wang, Haichao
通讯作者：
Wang, Haichao
影响因子：
2.9
作者：
Belayev, L;Busto, R;Ginsberg, MD
通讯作者：
Ginsberg, MD
影响因子：
4.8
作者：
Liu, Keyue;Mori, Shuji;Nishibori, Masahiro
通讯作者：
Nishibori, Masahiro
DOI：
10.1523/jneurosci.2435-08.2008
发表时间：
2008-11-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Muhammad S;Barakat W;Stoyanov S;Murikinati S;Yang H;Tracey KJ;Bendszus M;Rossetti G;Nawroth PP;Bierhaus A;Schwaninger M
通讯作者：
Schwaninger M