PDF(Pubmed)
Abstract：
Cancer-related cognitive impairment (CRCI) is a consequence of chemotherapy and extracranial radiation therapy (ECRT). Our prior work demonstrated gliosis in the brain following ECRT in SKH1 mice. The signals that induce gliosis were unclear. Right hindlimb skin from SKH1 mice was treated with 20 Gy or 30 Gy to induce subclinical or clinical dermatitis, respectively. Mice were euthanized at 6 h, 24 h, 5 days, 12 days, and 25 days post irradiation, and the brain, thoracic spinal cord, and skin were collected. The brains were harvested for spatial proteomics, immunohistochemistry, Nanostring nCounter® glial profiling, and neuroinflammation gene panels. The thoracic spinal cords were evaluated by immunohistochemistry. Radiation injury to the skin was evaluated by histology. The genes associated with neurotransmission, glial cell activation, innate immune signaling, cell signal transduction, and cancer were differentially expressed in the brains from mice treated with ECRT compared to the controls. Dose-dependent increases in neuroinflammatory-associated and neurodegenerative-disease-associated proteins were measured in the brains from ECRT-treated mice. Histologic changes in the ECRT-treated mice included acute dermatitis within the irradiated skin of the hindlimb and astrocyte activation within the thoracic spinal cord. Collectively, these findings highlight indirect neuronal transmission and glial cell activation in the pathogenesis of ECRT-related CRCI, providing possible signaling pathways for mitigation strategies.
摘要：
癌症相关的认知障碍（CRCI）是化疗和颅外放射治疗（ECRT）的结果。我们先前的工作证明了在SKH1小鼠中ECRT后大脑中的神经胶质增生。诱导神经胶质增生的信号尚不清楚。用20Gy或30Gy治疗SKH1小鼠的右后肢皮肤，以诱导亚临床或临床皮炎，分别。在6h时将小鼠安乐死，24h,5天,12天,照射后25天，和大脑，胸脊髓，并收集皮肤。大脑被收集用于空间蛋白质组学，免疫组织化学，NanostringnCounter®胶质分析，和神经炎症基因小组。通过免疫组织化学评估胸脊髓。通过组织学评估对皮肤的辐射损伤。与神经传递相关的基因，胶质细胞活化，先天免疫信号，细胞信号转导，与对照组相比，用ECRT治疗的小鼠的大脑中癌症差异表达。在ECRT处理的小鼠的大脑中测量了神经炎相关和神经退行性疾病相关蛋白的剂量依赖性增加。ECRT处理的小鼠的组织学变化包括后肢辐照皮肤内的急性皮炎和胸脊髓内的星形胶质细胞活化。总的来说，这些发现强调了ECRT相关CRCI发病机制中的间接神经元传递和神经胶质细胞活化,为缓解策略提供了可能的信号通路.
