1、SDF-1/CXCR7 Chemokine Signaling is Induced in the Peri-Infarct Regions in Patients with Ischemic StrokeSDF-1/CXCR7趋化因子在缺血性中风患者的周梗塞区域诱导纲要n Abstractn Image and Resultn Discussion n Acknowledgments1 AbstractAbstractStromal-derived factor-1 (SDF-1, also known as CXCL12) and its receptors CXCR4 and CXCR7
2、 play important roles in brain repair after ischemic stroke, as SDF-1/ CXCR4/CXCR7 chemokine signaling is critical for recruiting stem cells to sites of ischemic injury. Upregulation of SDF-1/CXCR4/CXCR7 chemokine signaling in the ischemic regions has been well-documented in the animal models of isc
3、hemic stroke, but not in human ischemic brain.由间质衍生的 fac-1( SDF-1,也称为 CXCL12)和它的受体 CXCR4和CXCR7在缺血性中风后在大脑修复中扮演着重要的角色,因为 SDF-1/CXCR4/CXCR7趋化因子对于在缺血性损伤的部位招募干细胞是至关重要的。在缺血性中风的动物模型中,在缺血性中风的动物模型中已经记录了 SDF-1/CXCR4/CXCR7的趋化因子,但在缺血性脑内却没有。AbstractHere, we found that protein expression of SDF-1 and CXCR7, but n
4、ot CXCR4, were significantly increased in the cortical peri-infarct regions (penumbra) after ischemic stroke in human, compared with adjacent normal tissues and control subjects.Double-label fluorescence immunohistochemistry shows that SDF-1 and CXCR4 proteins were expressed in neuronal cells and as
5、trocytes in the normal brain tissue and peri-infarct regions.在 这 里,我 们发现 ,与 邻 近的正常 组织 和 对 照 组 相比,在人 类 缺血性中 风 后的皮 质 周梗塞区域(半影)中, SDF-1和 CXCR7的蛋白质 表达,而不是 CXCR4, 显 著增加。双 标签荧 光免疫 组织 化学 显 示, SDF-1和 CXCR4蛋白 质 表达在正常 脑组织 和周 围 梗塞区域的神 经元 细 胞和星形胶 质细 胞中。AbstractCXCR7 protein was also observed in neuronal cells a
6、nd astrocytes in the normal cortical regions, but predominantly in astrocytes in the penumbra of ischemic brain. Our data suggest that ischemic stroke in human leads to an increase in the expression of SDF-1 and CXCR7, but not CXCR4, in the peri-infarct cerebral cortex. Our findings suggest that che
7、mokine SFD-1 is expressed not only in animal models of stroke, but also in the human brain after an ischemic injury. In addition, unlike animals, CXCR7 may be the primary receptor of SDF-1 in human stroke brain.在正常的皮质区域,也观察到 CXCR7蛋白质,但主要是在缺血性大脑的半影膜中的星形胶质细胞中。我们的数据表明,人类的缺血性中风导致了 SDF-1和 CXCR7的表达,而不是 CX
8、CR4,在梗塞的脑皮质中。我们的研究结果表明,趋化因子 SFD-1不仅表现在中风的动物模型中,而且在缺血性损伤后的人类大脑中也表现出来。此外,与动物不同的是,CXCR7可能是人类中风大脑中 SDF-1的主要受体。Image and Result2Image 1 Expression pattern of SDF-1/CXCR4/CXCR7 in post-stroke human brain. A) Representative images show that SDF-1 expression in cerebral cortex of infarcted brain. Top panel:
9、 low magnification; Bottom panel: high magnification. B) CXCR7 immunocytochemistry in the peri-infarct region (penumbra) and adjacent normal tissue. C) CXCR4 immunocytochemistry in the cortical penumbra and adjacent normal tissue.中风后人类大脑的 SDF-1/CXCR4/CXCR7的表达模式。 A)代表性的图像显示,在梗塞的大脑皮层中, SDF-1表达。前面板 :低放
10、大 ;底板 :高放大。 B)在梗塞部位(半乳)和邻近的正常组织中, CXCR7免疫细胞化学。 C)在皮质的半影和邻近的正常组织中, CXCR4免疫细胞化学。Image 2Phenotypes of SDF-1-positive cells in the human ischemic brain. A-B) Confocal image of representative immunofluorescent staining for NeuN (A) or GFAP (B) (Alexa Fluor 594, red), SDF-1 (Alexa Fluor 488, green), nucle
11、i (DAPI, blue), and merged image from adjacent normal regions of human ischemic stroke brain. C) Merged confocal images of double-label immunohistochemistry in the peri-infarct region (penumbra) of the human ischemic brain section using anti-GFAP (green) and anti-SDF-1 (red). D) Merged confocal imag
12、es of double-label immunohistochemistry in the penumbra on the human ischemic brain using anti-NeuN (red) and anti-SDF-1 (green). DAPI (blue) was used for nuclei counterstains.Image 3n Phenotypes of CXCR7-positive cells in the human ischemic brain. A) Merged confocal image of double-label immunohist
13、ochemistry on the normal region of the human ischemic brain section using anti-NeuN (red) and anti- CXCR7 (green). B) Merged confocal image of double-label immunohistochemistry on the normal region of the human ischemic brain section using anti-GFAP (red) and anti- CXCR7 (green). C) Double immunocytochemistry was performed on the ischemic brain sections in the penumbra using anti-GFAP (red) and anti-CXCR7 (green). The images were recorded using a 2-photon confocal microscope. D) Higher magnification view of merged confocal image in panel C. DAPI (blue) was used for nuclei counterstains.