Song G, Luo T, Dong L, Liu Q
Department of Radiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Department of Radiology, The Secondary Affiliated Hospital, Baotou Medical College, Baotou, Inner Mongolia, China.
Braz J Med Biol Res. 2017 Jul 3;50(7):e5403. doi: 10.1590/1414-431X20175403.
Solution reflux and edema hamper the convection-enhanced delivery of the standard treatment for glioma. Therefore, a real-time magnetic resonance imaging (MRI) method was developed to monitor the dosing process, but a quantitative analysis of local diffusion and clearance parameters has not been assessed. The objective of this study was to compare diffusion into the extracellular space (ECS) at different stages of rat C6 gliomas, and analyze the effects of the extracellular matrix (ECM) on the diffusion process. At 10 and 20 days, after successful glioma modeling, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was introduced into the ECS of rat C6 gliomas. Diffusion parameters and half-life of the reagent were then detected using MRI, and quantified according to the mathematical model of diffusion. The main ECM components [chondroitin sulfate proteoglycans (CSPGs), collagen IV, and tenascin C] were detected by immunohistochemical and immunoblot analyses. In 20-day gliomas, Gd-DTPA diffused more slowly and derived higher tortuosity, with lower clearance rate and longer half-life compared to 10-day gliomas. The increased glioma ECM was associated with different diffusion and clearance parameters in 20-day rat gliomas compared to 10-day gliomas. ECS parameters were altered with C6 glioma progression from increased ECM content. Our study might help better understand the glioma microenvironment and provide benefits for interstitial drug delivery to treat brain gliomas.
溶液反流和水肿阻碍了胶质瘤标准治疗的对流增强递送。因此，开发了一种实时磁共振成像（MRI）方法来监测给药过程，但尚未对局部扩散和清除参数进行定量分析。本研究的目的是比较大鼠C6胶质瘤不同阶段细胞外间隙（ECS）中的扩散情况，并分析细胞外基质（ECM）对扩散过程的影响。在成功建立胶质瘤模型后的第10天和第20天，将钆-二乙烯三胺五乙酸（Gd-DTPA）引入大鼠C6胶质瘤的ECS中。然后使用MRI检测试剂的扩散参数和半衰期，并根据扩散数学模型进行量化。通过免疫组织化学和免疫印迹分析检测主要的ECM成分[硫酸软骨素蛋白聚糖（CSPG）、IV型胶原和腱生蛋白C]。与10天的胶质瘤相比，在20天的胶质瘤中，Gd-DTPA扩散更慢，曲折度更高，清除率更低，半衰期更长。与10天的胶质瘤相比，20天大鼠胶质瘤中增加的胶质瘤ECM与不同的扩散和清除参数相关。随着C6胶质瘤进展，ECS参数因ECM含量增加而改变。我们的研究可能有助于更好地理解胶质瘤微环境，并为间质药物递送治疗脑胶质瘤提供帮助。
