论文标题
在11.7 t的扩散加权磁共振光谱探测的Cuprizone小鼠模型中的炎症驱动的神经胶质变化
Inflammation-driven glial alterations in the cuprizone mouse model probed with diffusion-weighted magnetic resonance spectroscopy at 11.7 T
论文作者
论文摘要
脑组织的炎症是免疫系统对存在有毒化合物或细胞损伤的复杂反应,导致一系列包括神经胶质细胞激活的病理过程。神经胶质反应性的无创磁共振成像标记对于体内检测和监测大脑炎症过程以及评估个性化处理的功效。由于它们在神经胶质细胞中的特定位置,肌醇(分钟)和胆碱化合物(TCHO)似乎是探测神经胶质特异性细胞内隔室的最佳候选者。但是,它们使用常规质子磁共振光谱(MRS)对其浓度进行了定量,这并不是针对炎症的特异性。相比之下,最近有人提出,在反应性星形胶质细胞的小鼠模型中,使用扩散加权MRS(DW-MR)测量的细胞内扩散可能是星形胶质肥大的特定标记。为了评估炎症驱动的神经胶质变化的分钟和TCHO扩散的特异性,我们在6周中毒后在丘比亚酮喂养的小鼠的call体中进行了DW-MR,并评估了使用免疫化学化学化学的星形胶质细胞和小胶质细胞改变的程度。与对照小鼠相比,在库利酮喂养的小鼠中,Mins和Tcho明显的扩散系数均显着升高,而组织学评估证实存在严重的炎症。此外,分别与星形胶质细胞和小胶质细胞面积的组织学测量值分别显示了与星形胶质细胞和小胶质细胞区域分数的强度和中等相关性,这证实了DW-MRS是在病理条件下特异性检测神经胶质变化的有希望的工具。
Inflammation of brain tissue is a complex response of the immune system to the presence of toxic compounds or to cell injury, leading to a cascade of pathological processes that include glial cell activation. Noninvasive magnetic resonance imaging markers of glial reactivity would be very useful for in vivo detection and monitoring of inflammation processes in the brain, as well as for evaluating the efficacy of personalized treatments. Due to their specific location in glial cells, myo-inositol (mIns) and choline compounds (tCho) seem the best candidates for probing glial-specific intra-cellular compartments. However, their concentrations quantified using conventional proton magnetic resonance spectroscopy (MRS) are not specific for inflammation. In contrast, it has been recently suggested that mIns intra-cellular diffusion, measured using diffusion-weighted MRS (DW-MRS) in a mouse model of reactive astrocytes, could be a specific marker of astrocytic hypertrophy. In order to evaluate the specificity of both mIns and tCho diffusion to inflammation-driven glial alterations, we performed DW-MRS in the corpus callosum of cuprizone-fed mice after 6 weeks of intoxication and evaluated the extent of astrocytic and microglial alterations using immunohistochemistry. Both mIns and tCho apparent diffusion coefficients were significantly elevated in cuprizone-fed mice compared to control mice, while histologic evaluation confirmed the presence of severe inflammation. Additionally, mIns and tCho diffusion showed, respectively, strong and moderate correlations with histological measures of astrocytic and microglial area fractions, confirming DW-MRS as a promising tool for specific detection of glial changes under pathological conditions.