Molecular mechanisms of cell death in periventricular leukomalacia
Molecular mechanisms of cell death in periventricular leukomalacia
复制标题
DOI：
10.1212/01.wnl.0000224754.63593.c4
复制
发表时间：
2006-07-25
期刊：
影响因子：
9.9
通讯作者：
Sebire, G.
中科院分区：
文献类型：
--
作者：
Kadhim, H.;Khalifa, M.;Sebire, G.
目的：探讨脑室周围白质软化症（PVL）神经细胞死亡的细胞因子相关分子级联反应.研究方法：作者探索了PVL人脑中潜在的肿瘤坏死因子α（TNF α）信号通路，并进行了原位免疫组织化学研究，以寻找这些大脑中细胞因子受体的可能表达。他们还研究了可能与神经细胞毒性有关的分子的可能联系，特别是涉及亚硝化诱导的细胞凋亡的途径。结果：TNF α过表达与PVL受累区域p75 TNF α R2和p55 TNF α R1受体的免疫反应性相关。PVL区脑血管内皮细胞p75 TNF α R2标记强烈，而未检测到血管p55 TNF α R1免疫反应性。在许多白色实质细胞上检测到两种受体的免疫标记。相比之下，在取自非PVL区域的组织中，对任一受体均无免疫反应性。此外，在原位过度表达诱导型一氧化氮合酶被发现在PVL脑区，其中检测到凋亡细胞死亡。结论：p75 TNF α R2和p55 TNF α R1受体和一氧化氮可能与脑室周围白质软化的发病机制有关。
Objective: To investigate the cytokine- related molecular cascade leading to neural cell death in periventricular leukomalacia (PVL). Methods: The authors explored potential tumor necrosis factor alpha (TNF alpha) signaling pathways in human brains with PVL and conducted in situ immunohistochemical investigations to search for possible expression of cytokine receptors in these brains. They also investigated likely links to molecules potentially involved in neurocytotoxicity, particularly pathways involving nitrosative-induced apoptosis. Results: TNF alpha overexpression was associated with immune reactivity for p75TNF alpha R2 and p55TNF alpha R1 receptors in affected PVL areas. p75TNF alpha R2 labeling was intense on cerebrovascular endothelial cells in PVL areas, whereas no vascular p55TNF alpha R1 immunoreactivity was detected therein. Immune labeling for both receptors was detected on many white matter parenchymal cells. In contrast, there was no immune reactivity for either receptor in tissues taken from non-PVL areas. Additionally, in situ overexpression of inducible nitric oxide synthase was found in PVL brain regions where apoptotic cell death was detected. Conclusions: Both p75TNF alpha R2 and p55TNF alpha R1 receptors and nitric oxide may be implicated in the pathogenesis of periventricular leukomalacia.