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首页> 外文期刊>Journal of Neuroscience Methods >Regional convection-enhanced delivery of gadolinium-labeled albumin in the rat hippocampus in vivo.
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Regional convection-enhanced delivery of gadolinium-labeled albumin in the rat hippocampus in vivo.

机译：vivo对标记增强的白蛋白在大鼠海马体内的区域对流增强递送。

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摘要

Convection-enhanced delivery (CED) has emerged as a promising method of targeted drug delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate distribution is unclear. We have utilized this approach to study extracellular transport and distribution of a contrast agent in the hippocampus, a complex structure susceptible to CNS disorders. The magnetic resonance (MR) contrast agent diethylene triamene penta-acetic acid chelated gadolinium-labeled albumin (Gd-albumin), tagged with Evans blue dye, was directly infused (V(i)=5 microl) into the dorsal and ventral hippocampus of seven male Sprague-Dawley rats. The final distribution profile of the contrast agent, a product of CED and limited diffusion, was observed in vivo using high-resolution T1-weighted MR imaging at 11.1T. Dense cell layers, such as the granule cell layer of the dentate gyrus and the pyramidal cell layer of CA1, appeared to be barriers to transport of the tracer. Three-dimensional distribution shape and volume (V(d)) differences, between the dorsal and ventral hippocampus infusions, were determined from the MR images using a semi-automatic segmentation routine (dorsal V(d)=23.4+/-1.8 microl, ventral V(d)=36.4+/-5.1 microl). Finer structural detail of the hippocampus was obtained using a combination of histological analysis and fluorescence imaging. This study demonstrates that CED has the potential to target all regions of the hippocampus and that tracer distribution is influenced by infusion site, underlying structure and circuitry, and extent of backflow. Therefore, CED, combined with high-resolution MR imaging, may be a useful strategy for delivering therapeutics for the treatment of CNS disorders affecting the hippocampus.
机译：对流增强输送（CED）已成为治疗中枢神经系统（CNS）疾病的靶向药物输送的一种有前途的方法，但是脑结构对输注液分布的影响尚不清楚。我们已经利用这种方法研究了海马中一种造影剂在细胞外的运输和分布，海马是一种易受CNS疾病困扰的复杂结构。磁共振（MR）造影剂二亚乙基三胺五乙酸螯合g标记的白蛋白（Gd-白蛋白），标记有埃文斯蓝染料，直接（V（i）= 5 microl）注入大鼠的背侧和腹侧海马区七只雄性Sprague-Dawley大鼠。使用在11.1T的高分辨率T1加权MR成像在体内观察到了造影剂（CED和有限扩散的产物）的最终分布图。密集的细胞层，如齿状回的颗粒细胞层和CA1的锥体细胞层，似乎是示踪剂运输的障碍。使用半自动分割程序从MR图像确定背侧和腹侧海马输注之间的三维分布形状和体积（V（d））差异（背侧V（d）= 23.4 +/- 1.8 microl，腹V（d）= 36.4 +/- 5.1微升）。通过组织学分析和荧光成像相结合，获得了海马更精细的结构细节。这项研究表明，CED有潜力靶向海马的所有区域，示踪剂分布受输注部位，基础结构和电路以及回流程度的影响。因此，CED与高分辨率MR成像相结合，可能是一种有效的策略，可用于治疗影响海马体的CNS疾病。

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