减少神经元调亡是治疗缺血性脑中风的有效手段。研究表明，神经元表达趋化因子受体CX3CR1，且影响神经元的存活。但脑中风后，CX3CR1对神经元凋亡的调控和机制尚不清楚。我们的预实验结果发现：敲除CX3CR1可减少小鼠脑中风后神经元凋亡；CX3CR1缺失可减轻线粒体损伤；敲除CX3CR1可减少谷氨酸刺激后神经元的死亡。已证实谷氨酸诱导细胞死亡的主要机制是增加Ca2+内流，而Ca2+内流、线粒体损伤是中风后神经元凋亡的主要通路。据此，我们推测：CX3CR1表达上调，Ca2+内流增加，线粒体损伤，Caspase3激活是中风后神经元凋亡的新机制,而阻断CX3CR1表达可减轻中风后脑损伤。我们拟制备CX3CR1敲除鼠和野生鼠中风动物模型和缺血细胞模型，应用CX3CR1基因转染、细胞内钙显像、线粒体功能测定及免疫荧光等技术，从整体、细胞及分子水平证明我们的假说，为缺血性脑中风的治疗提供新思路和新靶点

Preventing neuronal apoptosis is a main therapeutic method for ischemia stroke.Studies showed that CX3CR1 is expressed by neurons and affects the neuronal survival. However, the role and mechnism of neuronal CX3CR1 in ischemia stroke is unknown. Our preliminary experiment found that CX3CR1 deficiency decreased neuronal apoptosis in mice stroke model, and also prevented mitochondrial function. In vitro,CX3CR1 deficiency prevented neurons from apoptosis induced by glutamate. It is proven that the main mechanism of glutamate inducing apoptosis is to increase calcium influx. And calcium influx and mitochondria damage play an very important role in neuronal apoptosis after ischemia stroke Therefore, we hypothesize that the upregulation of neuronal CX3CR1-calcium influx-mitochondia dysfunction-neuronal apoptosis is a new mechanism of ischemia brain injury, and knocking out or blocking CX3CR1 expression will attenuate brain injury.In this study, we will induce mice middle cerebral artery occlusion (MCAO) model and neuronal ischemia model (oxygen and glucose deprivation,OGD)，using the techniques of gene transfection, intracelluar calcium imaging, immunofluorescence staining and mitochondrail function measuring et al., to prove the hypothesis from different levels of organ, cell and molecule. This will be a new therapeutic target for ischemia stroke.