机构：[1]Department of Neurology and the BNI-ASU Center for Preclinical Imaging,Barrow Neurological Institute, St.Joseph’s Hospital and Medical Center, 350West Thomas Road, Phoenix, Arizona 85013, USA[2]Department of Neurology,Key Laboratory of Neurorepair and Regeneration, Tianjin and Ministry ofEducation and Tianjin Neurological Institute, Tianjin Medical UniversityGeneral Hospital, Tianjin 300052, China[3]Department of Neurosurgery, theFirst Affiliated Hospital of Kunming Medical University, Kunming 650031,China外科科室神经外科神经外一科（神经外科）昆明医科大学附属第一医院
Background: Chemokine (C-X3-C motif) ligand 1 (CX3CL1)/CX3C chemokine receptor 1 (CX3CR1) signaling is important in modulating the communication between neurons and resident microglia/migrated macrophages in the central nervous system (CNS). Although CX3CR1 deficiency is associated with an improved outcome following ischemic brain injury, the mechanism of this observation is largely unknown. The aim of this study was to investigate how CX3CR1 deficiency influences microglia/macrophage functions in the context of its protection following brain ischemia. Methods: Wild-type (WT) and CX3CR1-deficient (CX3CR1(-/-)) mice were subjected to transient middle cerebral artery occlusion (MCAO) and reperfusion. The ischemic brain damage was monitored by rodent high-field magnetic resonance imaging. Neurological deficit was assessed daily. Neuronal apoptotic death and reactive oxygen species (ROS) production were analyzed by immunostaining and live imaging. Activation/inflammatory response of microglia/macrophage were assessed using immunohistochemistry, flow cytometry, 5-bromo-2-deoxyuridine labeling, cytokine ELISA, and real-time PCR. Results: CX3CR1(-/-) mice displayed significantly smaller infarcts and less severe neurological deficits compared to WT controls, following MCAO. In addition, CX3CR1(-/-) MCAO mice displayed fewer apoptotic neurons and reduced ROS levels. Impaired CX3CR1 signaling abrogated the recruitment of monocyte-derived macrophages from the periphery, suppressed the proliferation of CNS microglia and infiltrated macrophage, facilitated the alternative activation (M2 state) of microglia/macrophages, and attenuated their ability to synthesize and release inflammatory cytokines. Conclusion: Our results suggest that inhibition of CX3CR1 signaling could function as a therapeutic modality in ischemic brain injury, by reducing recruitment of peripheral macrophages and expansion/activation of CNS microglia and macrophages, resulting in protection of neurological function.
基金：
National Basic Science Program of China (2013CB966900), National Natural
Science Foundation of China (81230028 and 81360204), National Key Project
of Clinical Neurology of China, US National Institutes of Health (R01AI083294,
R01NS082745 and R21NS082902) and the American Heart Association
(GRNT18970031).
第一作者机构：[1]Department of Neurology and the BNI-ASU Center for Preclinical Imaging,Barrow Neurological Institute, St.Joseph’s Hospital and Medical Center, 350West Thomas Road, Phoenix, Arizona 85013, USA[3]Department of Neurosurgery, theFirst Affiliated Hospital of Kunming Medical University, Kunming 650031,China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Zhiwei Tang,Yan Gan,Qiang Liu,et al.CX3CR1 deficiency suppresses activation and neurotoxicity of microglia/macrophage in experimental ischemic stroke[J].JOURNAL OF NEUROINFLAMMATION.2014,11:doi:10.1186/1742-2094-11-26.
APA：
Zhiwei Tang,Yan Gan,Qiang Liu,Jun-Xiang Yin,Qingwei Liu...&Fu-Dong Shi.(2014).CX3CR1 deficiency suppresses activation and neurotoxicity of microglia/macrophage in experimental ischemic stroke.JOURNAL OF NEUROINFLAMMATION,11,
MLA：
Zhiwei Tang,et al."CX3CR1 deficiency suppresses activation and neurotoxicity of microglia/macrophage in experimental ischemic stroke".JOURNAL OF NEUROINFLAMMATION 11.(2014)
医学