Mammalian transmissible spongiform encephalopathies (TSEs) display marked activation of astrocytes and microglia that precedes neuronal loss. Investigation of clinical parallels between TSEs and other neurodegenerative protein misfolding diseases, such as Alzheimer's disease, has revealed similar patterns of neuroinflammatory responses to the accumulation of self-propagating amyloids. The contribution of glial activation to the progression of protein misfolding diseases is incompletely understood, with evidence for mediation of both protective and deleterious effects. Glial populations are heterogeneously distributed throughout the brain and capable of dynamic transitions along a spectrum of functional activation states between pro- and antiinflammatory polarization extremes. Using a murine model of Rocky Mountain Laboratory scrapie, the neuroinflammatory response to prion infection was characterized by evaluating glial activation across 15 brain regions over time and correlating it to traditional markers of prion neuropathology, including vacuolation and PrPSc deposition. Quantitative immunohistochemistry was used to evaluate glial expression of iNOS and Arg1, markers of classical and alternative glial activation, respectively. The results indicate progressive upregulation of iNOS in microglia and a mixed astrocytic profile featuring iNOS expression in white matter tracts and detection of Arg1-positive populations throughout the brain. These data establish a temporospatial lesion profile for this prion infection model and demonstrate evidence of multiple glial activation states.

中文翻译：

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对Pri病毒感染的神经胶质反应的原位颞pat特征。

哺乳动物可传播的海绵状脑病（TSE）在神经元丧失之前显示出星形胶质细胞和小胶质细胞的明显活化。对TSE和其他神经退行性蛋白质错误折叠疾病（例如阿尔茨海默氏病）之间的临床相似性的调查显示，对自我繁殖的淀粉样蛋白积累的神经炎症反应的模式相似。胶质细胞活化对蛋白质错误折叠疾病进展的贡献尚不完全清楚，有证据表明介导了保护性和有害性作用。胶质细胞群体在大脑中异质分布，并且能够在促炎和抗炎性极化极端之间沿着一系列功能激活状态动态转变。使用落基山实验室瘙痒病的鼠模型，通过评估随时间变化的15个大脑区域的神经胶质激活并将其与brain病毒神经病理学的传统标记（包括空泡化和PrPSc沉积）相关联，来表征对病毒感染的神经炎症反应。定量免疫组织化学分别用于评估神经胶质表达的iNOS和Arg1，分别为经典和替代神经胶质激活的标志。结果表明，小胶质细胞中iNOS的进行性上调和混合的星形胶质细胞特征，其中iNOS在白质物质中表达，并且在整个大脑中检测到Arg1阳性人群。这些数据为该病毒感染模型建立了颞pat部病变概况，并证明了多种神经胶质激活状态的证据。