Date Published: April 1, 2018
Publisher: JKL International LLC
Author(s): Yu Zhang, Hongxia Zhang, Siyang Lin, Xudong Chen, Yu Yao, XiaoOu Mao, Bei Shao, Qichuan Zhuge, Kunlin Jin.
Stromal-derived factor-1 (SDF-1, also known as CXCL12) and its receptors CXCR4 and CXCR7 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 ischemic stroke, but not in human ischemic brain. Here, we found that protein expression of SDF-1 and CXCR7, but not 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 astrocytes in the normal brain tissue and peri-infarct regions. CXCR7 protein was also observed in neuronal cells and 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 chemokine 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.
To determine the expression pattern of SDF-1 protein, immunocytochemistry was performed on the ischemic brain sections from patients with ischemic stroke using anti-SDF-1 antibody. As shown in Fig. 1A, SDF-1-immunopositive cells were predominantly localized in the cortical peri-infarct region (penumbra) and infarct area, but a little in the adjacent normal region in brain specimens of stroke patients, suggesting that SDF-1 protein is induced in the ischemic regions after ischemic stroke. Next, we examined the expression patterns of second SDF-1 receptor CXCR7, Like SDF-1, CXCR7 protein expression was significantly increased in the penumbra of human ischemic brain, compared with the adjacent normal regions. However, the expression of CXCR7 was low in the infarct core (Fig. 1B). Interestingly, the expression of CXCR4 protein in the cortical penumbra was not significantly increased, compared with the adjacent normal region, and essentially absent from the infarct core (Fig. 1C). These findings suggest that CXCR7, rather than CXCR4, is the primary receptor for SDF1 in the ischemic brain in human.
The major finding of this study is 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 compared with the adjacent normal brain and ischemic core.