AUTHOR=Fang Yuan , Dong Yanchao , Zheng Tao , Du Dan , Wen Jiexia , Gao Dawei , Liu Lanxiang 

TITLE=Altered Tracer Distribution and Clearance in the Extracellular Space of the Substantia Nigra in a Rodent Model of Parkinson's Disease

JOURNAL=Frontiers in Neuroscience

VOLUME=11

YEAR=2017

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2017.00409

DOI=10.3389/fnins.2017.00409

ISSN=1662-453X

ABSTRACT=<p>The relationship between extracellular space (ECS) diffusion parameters and brain drug clearance is not well-studied, especially in the context of Parkinson's disease (PD). Therefore, we used a rodent model of PD to explore the distribution and clearance of a magnetic resonance tracer. Forty male Sprague Dawley rats were randomized into four different groups: a PD group, a Madopar group (PD + Madopar treatment), a sham group, and a control group. All rats received an injection of the extracellular tracer gadolinium-diethylene triaminepentacetic acid (Gd-DTPA) directly into the substantia nigra (SN). ECS diffusion parameters including the effective diffusion coefficient (D<sup>*</sup>), clearance coefficient (k'), ratio of the maximum distribution volume of the tracer (Vd-max%), and half-life (t<sub>1/2</sub>) were measured. We found that all parameters were significantly increased in the PD group compared to the other three groups (D<sup>*</sup>: <italic>F</italic> = 5.774, <italic>p</italic> = 0.0025; k': <italic>F</italic> = 20.00, <italic>P</italic> &lt; 0.0001; Vd-max%: <italic>F</italic> = 12.81, <italic>P</italic> &lt; 0.0001; and t<sub>1/2</sub>: <italic>F</italic> = 23.35, <italic>P</italic> &lt; 0.0001). In conclusion, the PD group exhibited a wider distribution and lower clearance of the tracer compared to the other groups. Moreover, k' was more sensitive than D<sup>*</sup> for monitoring morphological and functional changes in the ECS in a rodent model of PD.</p>