Altered tracer distribution and clearance in the extracellular space of the substantia nigra in a rodent model of Parkinson's disease

Abstract

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*), clearance coefficient (k'), ratio of the maximum distribution volume of the tracer (Vd-max%), and half-life (t1/2) were measured. We found that all parameters were significantly increased in the PD group compared to the other three groups (D*: F = 5.774, p = 0.0025; k': F = 20.00, P < 0.0001; Vd-max%: F = 12.81, P < 0.0001; and t1/2: F = 23.35, P < 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* for monitoring morphological and functional changes in the ECS in a rodent model of PD.