Delayed expressed TNFR1 co-localize with ICAM-1 in astrocyte in mice brain after transient focal ischemia
Delayed expressed TNFR1 co-localize with ICAM-1 in astrocyte in mice brain after transient focal ischemia
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DOI：
10.1016/j.neulet.2004.07.083
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发表时间：
2004-11
影响因子：
2.5
通讯作者：
L. Yin;H. Ohtaki;T. Nakamachi;Yoshifumi Kudo;R. Makino;S. Shioda
中科院分区：
文献类型：
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作者：
L. Yin;H. Ohtaki;T. Nakamachi;Yoshifumi Kudo;R. Makino;S. Shioda
细胞间粘附分子-1（ICAM-1）在脑缺血后表达，并参与诱导神经元细胞死亡。最近，我们报道了ICAM-1在缺血慢性期定位于星形胶质细胞。然而，星形胶质细胞ICAM-1在脑缺血后的调节尚未详细阐明。因此，我们采用真实的时间PCR和免疫组化方法检测了短暂性大脑中动脉闭塞（tMCAO）后TNFR 1基因和蛋白的表达。此外，我们还研究了缺血慢性期星形胶质细胞中TNFR 1和ICAM-1的关系。TNFR 1 mRNA在缺血时表达轻度增加，再灌注12 h表达显著增加。在正常动物的皮质中观察到很少的TNFR 1样免疫反应性（TNFR 1-LI）。而缺血中心区TNFR 1-LI在缺血1h即开始升高，3- 6 h下降，再灌注12- 24 h再次升高。再灌注24 h后，神经元和星形胶质细胞中均可见TNFR 1阳性表达，少突胶质细胞和小胶质/巨噬细胞中未见TNFR 1阳性表达。tMCAO后96小时，病灶周围区TNFR 1-LI增加，并出现星形胶质细胞样细胞。采用免疫双标法，发现ICAM-1-LI与GFAP-LI重叠。我们的数据表明，TNFR 1的表达上调，根据缺血损伤和延迟表达TNFR 1-LI与ICAM-1-LI共定位在星形胶质细胞后tMCAO。提示星形胶质细胞ICAM-1受TNF-α依赖性通路调节。
Intercellular adhesion molecule-1 (ICAM-1) is expressed after brain ischemia and is participated in the induction of neuronal cell death. Recently, we have reported that ICAM-1 is localized in astrocytes in the chronic phase of ischemia. However, the regulation of astroglial ICAM-1 after brain ischemia is not elucidated in detail. Therefore, we examined the gene and protein expression of TNFR1 after transient middle cerebral artery occlusion (tMCAO) by using real time-PCR and immunohistochemistry. Moreover, we determined the relationship of TNFR1 and ICAM-1 in the astrocyte in chronic phase of ischemia. Increased expression of TNFR1 mRNA in the ipsilateral cortex was noted slightly during ischemia and was significantly increased at 12h after reperfusion. Few TNFR1-like imuunoreactivity (TNFR1-LI) was observed in the cortex of normal animals. However, TNFR1-LI was increased at 1h during ischemia, then it was decreased at 3–6h, and was increased again at 12–24h after reperfusion in the core of ischemic area. TNFR1-LI was demonstrated in both neurons and astrocytes but not in oligodendrocytes and microglia/macrophages at 24h after reperfusion. At 96h after tMCAO, TNFR1-LI was increased in the perifocal region and it appeared to be displayed the astrocyte-like cells. By use of double immunostaining method, we found that the ICAM-1-LI was overlapped with GFAP-LI. Our data indicates that the expression of TNFR1 is up-regulated in accordance with ischemic insult and delayed expressed TNFR1-LI co-localized with ICAM-1-LI in astrocytes after tMCAO. These results suggest that astroglial ICAM-1 is regulated by TNF-α dependent pathway.