Troakes Claire, Smyth Rachel, Noor Farzana, Maekawa Satomi, Killick Richard, King Andrew, Al-Sarraj Safa
Basic and Clinical Neuroscience Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Old Age Psychiatry Department, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Neuropathology. 2017 Feb;37(1):12-24. doi: 10.1111/neup.12320. Epub 2016 Jul 1.
There is mounting evidence linking traumatic brain injury (TBI) to neurodegeneration. Clusterin (apolipoprotein J or ApoJ) is a complement inhibitor that appears to have a neuroprotective effect in response to tissue damage and has been reported to be upregulated in Alzheimer's disease. Here we investigated the time course and cellular expression pattern of clusterin in human TBI. Tissue from 32 patients with TBI of varying survival times (from under 30 min to 10 months) was examined using immunohistochemistry for clusterin alongside other markers of neurodegeneration and neuroinflammation. TBI cases were compared to ischemic brain damage, Alzheimer's disease and controls. Double immunofluorescence was carried out in order to examine cellular expression. Clusterin was initially expressed in an axonal location less than 30 min following TBI and increased in intensity and the frequency of deposits with increasing survival time up to 24 h, after which it appeared to reduce in intensity but was still evident several weeks after injury. Clusterin was first evident in astrocytes after 45 min, being increasingly seen up to 48 h but remaining intense in TBI cases with long survival times. Our results suggest clusterin plays a role in modulating the inflammatory response of acute and chronic TBI and that it is a useful marker for TBI, particularly in cases with short survival times. Its prominent accumulation in astrocytes, alongside a mounting inflammatory response and activation of microglial cells supports a potential role in the neurodegenerative changes that occur as a result of TBI.
越来越多的证据表明创伤性脑损伤（TBI）与神经退行性变有关。簇集蛋白（载脂蛋白J或ApoJ）是一种补体抑制剂，似乎对组织损伤具有神经保护作用，并且据报道在阿尔茨海默病中上调。在此，我们研究了簇集蛋白在人类TBI中的时间进程和细胞表达模式。使用免疫组织化学方法对32例不同生存时间（从不到30分钟到10个月）的TBI患者的组织进行检测，以检测簇集蛋白以及其他神经退行性变和神经炎症标志物。将TBI病例与缺血性脑损伤、阿尔茨海默病及对照组进行比较。进行双重免疫荧光检测以检查细胞表达。TBI后不到30分钟，簇集蛋白最初在轴突部位表达，随着生存时间延长至24小时，其沉积强度和频率增加，此后强度似乎降低，但在损伤后数周仍很明显。45分钟后，簇集蛋白首先在星形胶质细胞中明显可见，直至48小时越来越多地被观察到，但在生存时间长的TBI病例中仍保持高强度。我们的数据表明，簇集蛋白在调节急性和慢性TBI的炎症反应中起作用，并且它是TBI的一个有用标志物，特别是在生存时间短的病例中。它在星形胶质细胞中的显著积累，以及炎症反应的增加和小胶质细胞的激活，支持了其在TBI导致的神经退行性变变化中的潜在作用。
