In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space
In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space
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DOI：
10.1073/pnas.0509425103
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发表时间：
2006-04-04
影响因子：
11.1
通讯作者：
Nicholson, C
中科院分区：
文献类型：
--
作者：
Thorne, RG;Nicholson, C
脑细胞外间隙（ECS）内的扩散对于化学信号传导以及神经元和神经胶质细胞获取营养物质和治疗药物是必要的;然而，活组织中ECS的宽度仍然未知。我们使用集成光学成像显示，葡聚糖和水溶性量子点与斯托克斯-爱因斯坦直径大至35 nm的成年大鼠体内新皮层的ECS内扩散。将ECS建模为充满流体的“孔”，预测正常宽度为38-64 nm，比固定组织的EM估计值大至少2倍。终末缺血后，ECS宽度福尔斯下降到10 nm以下，这可能是电子显微照片中可见的小ECS的解释。我们的研究结果将改善溢出和异位释放后神经递质扩散的建模，并建立药物递送载体（如病毒，脂质体和纳米颗粒）在脑ECS中扩散的尺寸限制。
Diffusion within the extracellular space (ECS) of the brain is necessary for chemical signaling and for neurons and glia to access nutrients and therapeutics; however, the width of the ECS in living tissue remains unknown. We used integrative optical imaging to show that dextrans and water-soluble quantum dots with Stokes-Einstein diameters as large as 35 nm diffuse within the ECS of adult rat neocortex in vivo. Modeling the ECS as fluid-filled '' pores '' predicts a normal width of 38-64 nm, at least 2-fold greater than estimates from EM of fixed tissue. ECS width falls below 10 nm after terminal ischemia, a likely explanation for the small ECS visualized in electron micrographs. Our results will improve modeling of neurotransmitter spread after spillover and ectopic release and establish size limits for diffusion of drug delivery vectors such as viruses, liposomes, and nanoparticles in brain ECS.