Chronic neuroinflammation and cognitive impairment following transient global cerebral ischemia: role of fractalkine/CX3CR1 signaling.
Chronic neuroinflammation and cognitive impairment following transient global cerebral ischemia: role of fractalkine/CX3CR1 signaling.
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DOI：
10.1186/1742-2094-11-13
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发表时间：
2014-01-22
影响因子：
9.3
通讯作者：
Wadowska M
中科院分区：
文献类型：
--
作者：
Briones TL;Woods J;Wadowska M
虽然在脑缺血的动物模型中已经广泛地研究了神经炎症，但是它们的对比功能仍然没有完全理解。神经炎症的主要参与者是小胶质细胞和小胶质细胞活化，通常由趋化因子CX 3CL 1（fractalkine）及其受体CX 3CR 1调节。在这里，我们研究了CX 3CR 1对缺血诱导的慢性神经炎症和认知功能的参与，使用小干扰RNA（siRNA）。研究中包括40只成年雄性Wistar大鼠，并接受缺血或假手术，然后在再灌注后7天开始随机接受CX 3CR 1 siRNA或乱序RNA作为对照。在siRNA递送后28天开始行为测试，并且在行为测试后对所有大鼠实施安乐死。我们的数据显示：（i）短暂性全脑缺血显著降低了海马中的fractalkine/CX 3CR 1信号传导;（ii）CX 3CR 1功能的抑制加剧了缺血诱导的小胶质细胞活化和促炎细胞因子水平的慢性增加;（iii）CX 3CR 1功能的抑制恶化了缺血诱导的慢性认知障碍;（iv）在假手术大鼠中抑制CX 3CR 1功能导致IL-1β表达增加和行为表现受损。然而，没有观察到CX 3CR 1对缺血诱导的神经变性的显著作用。本研究为了解CX 3CR 1在慢性神经炎症和认知障碍中的作用提供了重要的见解。
Although neuroinflammation has been studied extensively in animal models of cerebral ischemia, their contrasting functions are still not completely understood. A major participant in neuroinflammation is microglia and microglial activation usually regulated by the chemokine CX3CL1 (fractalkine) and its receptor, CX3CR1. Here, we examined the involvement of CX3CR1 on ischemia-induced chronic neuroinflammation and cognitive function using small interfering RNA (siRNA). Forty adult male Wistar rats were included in the study and received either ischemia or sham surgery then were randomized to receive either CX3CR1 siRNA or scrambled RNA as control starting at 7 days after reperfusion. Behavioral testing commenced 28 days after siRNA delivery and all rats were euthanized after behavioral testing. Our data showed that: (i) transient global cerebral ischemia significantly decreased fractalkine/CX3CR1 signaling in the hippocampus; (ii) inhibition of CX3CR1 function exacerbated the ischemia-induced chronic increase in microglial activation and pro-inflammatory cytokine levels; (iii) inhibition of CX3CR1 function worsened ischemia-induced chronic cognitive impairment; (iv) inhibition of CX3CR1 function in sham rats resulted in increased IL-1β expression and impaired behavioral performance. However, no significant effect of CX3CR1 on ischemia-induced neurodegeneration was seen. The present study provides important insight to understanding the involvement of CX3CR1 in chronic neuroinflammation and cognitive impairment.
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影响因子：
5.3
作者：
Cipriani, Raffaela;Villa, Pia;Limatola, Cristina
通讯作者：
Limatola, Cristina
DOI：
10.1073/pnas.95.18.10896
发表时间：
1998-09-01
影响因子：
11.1
作者：
Harrison, JK;Jiang, Y;Feng, LL
通讯作者：
Feng, LL
影响因子：
3.5
作者：
Hassani, Z;Lemkine, GF;Demeneix, BA
通讯作者：
Demeneix, BA
影响因子：
6.2
作者：
Fumagalli, Stefano;Perego, Carlo;De Simoni, Maria-Grazia
通讯作者：
De Simoni, Maria-Grazia
影响因子：
2.4
作者：
Lourbopoulos, A.;Grigoriadis, N.;Simeonidou, C.
通讯作者：
Simeonidou, C.