Imaging and Quantitative Analysis of the Interstitial Space in the Caudate Nucleus in a Rotenone-Induced Rat Model of Parkinson's Disease Using Tracer-based MRI.

Yu Fu,Jingbo Li,Deyong Lv,Wei Wang,Hongfu Li

doi:10.14336/ad.2016.0625

Abstract

Parkinson’s disease (PD) is characterized by pathological changes within several deep structures of the brain, including the substantia nigra and caudate nucleus. However, changes in interstitial fluid (ISF) flow and the microstructure of the interstitial space (ISS) in the caudate nucleus in PD have not been reported. In this study, we used tracer-based magnetic resonance imaging (MRI) to quantitatively investigate the alterations in ISS and visualize ISF flow in the caudate nucleus in a rotenone-induced rat model of PD treated with and without madopar. In the rotenone-induced rat model, the ISF flow was slowed and the tortuosity of the ISS was significantly decreased. Administration of madopar partially prevented these changes of ISS and ISF. Therefore, our data suggest that tracer-based MRI can be used to monitor the parameters related to ISF flow and ISS microstructure. It is a promising technique to investigate the microstructure and functional changes in the deep brain regions of PD.

Highlights

The interstitial space (ISS) within the brain provides an immediate accommodation space for neural cells and contributes to the physiological and functional homeostasis of the brain, where the flow of interstitial fluid (ISF) is important for nutrient supply, waste removal and intercellular communication [1]
In this study, using tracer-based magnetic resonance imaging (MRI) allowed us for the first time to visualize the changes in ISF flow in the caudate nucleus in the rotenone-induced rat model of Parkinson’s disease (PD)
We demonstrated that the ISF flow slowed and that the tortuosity of the ISS significantly decreased in the rat model

Summary

Introduction

The interstitial space (ISS) within the brain provides an immediate accommodation space for neural cells and contributes to the physiological and functional homeostasis of the brain, where the flow of interstitial fluid (ISF) is important for nutrient supply, waste removal and intercellular communication [1]. Studies have demonstrated microstructural changes in the ISS of PD [5, 6]. The caudate nucleus is vulnerable to the effects of PD and is the target region of several promising therapeutic strategies [7, 8]. Investigating the changes in ISS and ISF flow in the caudate nucleus is necessary to comprehensively understand the mechanisms underlying pathogenesis of PD and optimize the efficacy of therapeutic strategies. Imaging the Interstitial Space in PD brain Using Tracer-based MRI technique is a unique in vivo method that can measure both the microstructure of ISS and ISF flow in deep brain regions [10, 11]. We investigated the changes of ISS in the caudate nucleus in a rotenone-induced model of PD, with or without madopar treatment, using tracer-based MRI

Methods

Results

Conclusion