Characterization of osteopontin expression and function after status epilepticus
Characterization of osteopontin expression and function after status epilepticus
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DOI：
10.1111/j.1528-1167.2008.01613.x
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发表时间：
2008-10-01
期刊：
影响因子：
5.6
通讯作者：
Dingledine, Raymond
中科院分区：
文献类型：
--
作者：
Borges, Karin;Gearing, Maria;Dingledine, Raymond
目的：骨桥蛋白是一种存在于多种组织中的细胞因子，在组织损伤和修复中起重要作用。本研究有两个目的：表征癫痫持续状态（SE）后骨桥蛋白的表达，并验证骨桥蛋白影响癫痫发作易感性或改变SE后细胞死亡和炎症的假设。方法：采用匹罗卡品诱导OPN-/-和OPN+/+小鼠SE，比较癫痫易感性、炎症基因实时PCR等神经病理指标和骨桥蛋白免疫组化。研究了添加骨桥蛋白对n -甲基- d -天冬氨酸对ONP-/-小鼠神经细胞兴奋毒性的影响。结果：退行性神经元在SE后2 ~ 3天出现骨桥蛋白免疫反应。10 ~ 31天后，丘脑退化轴突骨桥蛋白呈阳性。匹罗卡品、氟乙基和最大电休克模型中OPN-/-和OPN+/+小鼠对癫痫发作的易感性相似。在匹罗卡品诱导SE后的神经元损伤程度、几种神经病理标记物的表达或选定炎症基因的RNA水平上，均无显著差异。重组和天然牛骨桥蛋白不影响nmda诱导的OPN-/-小鼠神经元细胞死亡的程度。结论：我们证明骨桥蛋白在海马不同的时间序列中响应SE上调，特别是在退行性神经元和轴突中。然而，骨桥蛋白在SE后的前3天内似乎没有调节神经退行性变或炎症。
Purpose: Osteopontin is a cytokine found in many tissues and plays a role in tissue injury and repair. This study had two goals: to characterize osteopontin expression after status epilepticus (SE), and to test the hypotheses that osteopontin affects the susceptibility to seizures or alters cell death and inflammation after SE.Methods: Pilocarpine was used to induce SE in OPN-/- and OPN+/+ mice to compare seizure susceptibility, neuropathological markers including real time PCR for inflammatory genes, and osteopontin immunohistochernistry. The effect of added osteopontin on excitotoxicity by N-methyl-D-aspartate in neuronal cultures of ONP-/- mice was determined.Results: Neurons undergoing degeneration showed osteopontin immunoreactivity 2-3 days after SE. After 10 to 31 days degenerating axons in the thalamus were osteoponti n -positive. The susceptibility to seizures of OPN-/- and OPN+/+ mice in the pilocarpine, fluorothyl, and maximal electroshock models was similar. There were no significant differences in the extent of neuronal damage after pilocarpine-induced SE, the expression of several neuropathological markers or the RNA levels of selected inflammatory genes. Recombinant and natural bovine osteopontin did not affect the extent of NMDA-induced cell death in OPN-/- mouse neuronal cultures.Conclusion: We demonstrated that osteopontin is up-regulated in response to SE in distinct temporal sequences in the hippocampus, specifically in degenerating neurons and axons. However, osteopontin did not appear to regulate neurodegeneration or inflammation within the first 3 days after SE.