Two region-dependent pathways of eosinophilic neuronal death after transient cerebral ischemia
Two region-dependent pathways of eosinophilic neuronal death after transient cerebral ischemia
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DOI：
10.1111/j.1440-1789.2008.00939.x
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发表时间：
2009-02-01
期刊：
影响因子：
2.3
通讯作者：
Mizusawa, Hidehiro
中科院分区：
文献类型：
--
作者：
Sun, Liyuan;Kuroiwa, Toshihiko;Mizusawa, Hidehiro
在缺血后的脑中发现了各种类型的嗜酸性神经元（EN）。我们检测了缺血皮质核心区和周边区EN的时间分布，并分析了其与各种细胞死亡相关因子表达的关系。蒙古沙土鼠单侧前脑缺血引起的短暂的颈总动脉闭塞，并从3 h至2周缺血后的大脑准备的EN的形态计量学和免疫组化分析。EN与最低限度的异常核和肿胀的细胞体出现在3 h的缺血核心和周围在12 h。在这两个位置，多种细胞死亡相关因子，包括钙，μ-钙蛋白酶，组织蛋白酶D，78 kDa葡萄糖调节蛋白（GRP 78）和泛素被激活。在缺血核心，固缩和不规则萎缩的细胞质在12小时达到峰值，这是与显着增加染色钙和μ-钙蛋白酶。细胞核固缩、胞浆稀少的EN在第4天达到高峰，TUNEL和钙染色阳性。在缺血周围，EN细胞胞浆轻度萎缩，并在1周内依次发生核固缩、核破裂和核溶解。这些细胞的TUNEL和钙染色阳性。所有类型的EN均为caspase 3阴性。脑缺血后EN变化可能有两种区域依赖性途径：核固缩伴核心区胞浆皱缩，核崩解伴周边区胞浆轻度萎缩。这种差异协调了EN中细胞死亡相关因子的不同激活模式。
Various types of eosinophilic neurons (ENs) are found in the post-ischemic brain. We examined the temporal profile of ENs in the core and peripheral regions of the ischemic cortex, and analyzed the relationship to the expression of various cell death-related factors. Unilateral forebrain ischemia was induced in Mongolian gerbils by transient common carotid artery occlusions, and the brains from 3 h to 2 weeks post-ischemia were prepared for morphometric and immunohistochemical analysis of ENs. ENs with minimally abnormal nuclei and swollen cell bodies appeared at 3 h in the ischemic core and at 12 h in the periphery. In both locations multiple cell death-related factors including calcium, mu-calpain, cathepsin D, 78 kDa glucose-regulated protein (GRP78) and ubiquitin were activated. In the ischemic core, pyknosis and irregularly atrophic cytoplasm peaked at 12 h, which was associated with significant increases in staining for calcium and mu-calpain. ENs with pyknosis and scant cytoplasm peaked at 4 days and were positive for TUNEL and calcium staining. In the ischemic periphery, ENs had slightly atrophic cytoplasm and sequentially developed pyknosis, karyorrhexis and karyolysis over 1 week. These cells were positive for TUNEL and calcium staining. All types of EN were negative for caspase 3. There may be two region-dependent pathways of EN changes in the post-ischemic brain: pyknosis with cytoplasmic shrinkage in the core, and nuclear disintegration with slightly atrophic cytoplasm in the periphery. This difference coordinates different activation patterns of cell death-related factors in ENs.