Role of the chemokine receptors CCR2 and CX3CR1 in an experimental model of thrombotic stroke
Role of the chemokine receptors CCR2 and CX3CR1 in an experimental model of thrombotic stroke
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DOI：
10.1016/j.bbi.2018.03.008
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发表时间：
2018-05-01
影响因子：
15.1
通讯作者：
Rivest, Serge
中科院分区：
文献类型：
--
作者：
Cisbani, Giulia;Le Behot, Audrey;Rivest, Serge
中风是全球第二大死亡原因，发生于脑血管破裂导致脑血液循环中断或局部血栓形成之后。缺血性损伤引发重要的炎症反应，其特征在于大量白细胞浸润、胶质细胞活化和神经血管重组。趋化因子及其受体，如CCR2和CX3CR1，在受损区域的白细胞募集中起重要作用。小鼠基因耗尽的两个受体CCR2和CX3CR1进行局灶性脑缺血，局部应用氯化铁截断远端大脑中动脉的基础上。仅限于皮质区域的梗塞在WT小鼠中保持稳定，而在转基因小鼠中随着时间的推移而减少。此外，我们没有观察到任何显着的变化，在梗死区的炎症反应的水平，而免疫细胞浸润和神经血管化调制根据基因型。我们的研究结果表明，CCR2和CX3CR1受体的基因缺失对脑永久性缺血具有神经保护作用。这项研究强调了CCR2和CX3CR1表达免疫细胞在与缺血性损伤相关的神经病理学中的关键作用。(C)2018爱思唯尔公司All rights reserved.
Stroke is the second cause of mortality worldwide and occurs following the interruption of cerebral blood circulation by cerebral vessel burst or subsequent to a local thrombus formation. Ischemic lesion triggers an important inflammatory response, characterized by massive infiltration of leukocytes, activation of glial cells and neurovascular reorganization. Chemokines and their receptors, such as CCR2 and CX3CR1, play an important role in leukocyte recruitment in the damaged area. Mice genetically depleted for the two receptors CCR2 and CX3CR1 underwent focal cerebral ischemia, based on the topical application of ferric chloride to truncate the distal middle cerebral artery. The infarct, limited only to the cortical area, remained stable in WT mice, while it is reduced overtime in the transgenic mice. Moreover, we did not observe any significant changes in the level of the inflammatory response in the infarcted areas while immune cell infiltration and neurovascularization are modulated according to genotype. Our results show that the genetic deletion of both CCR2 and CX3CR1 receptors has neuroprotective effects in response to a cerebral permanent ischemia. This study underlines a key role of CCR2- and CX3CR1-expressing immune cells in the neuropathology associated with ischemic injuries. (C) 2018 Elsevier Inc. All rights reserved.