The Mechanism of Downregulated Interstitial Fluid Drainage Following Neuronal Excitation.

Ze Teng,Ian Leigh Alberts,Hongbin Han,Xianjie Cai,Yuanyuan Li,Jun Yang,Guomei Zhao,Lan Yuan,Kuangyu Shi,Dehua Cui,Rui Wang

doi:10.14336/ad.2020.0224

Abstract

The drainage of brain interstitial fluid (ISF) has been observed to slow down following neuronal excitation, although the mechanism underlying this phenomenon is yet to be elucidated. In searching for the changes in the brain extracellular space (ECS) induced by electrical pain stimuli in the rat thalamus, significantly decreased effective diffusion coefficient (DECS) and volume fraction (α) of the brain ECS were shown, accompanied by the slowdown of ISF drainage. The morphological basis for structural changes in the brain ECS was local spatial deformation of astrocyte foot processes following neuronal excitation. We further studied aquaporin-4 gene (APQ4) knockout rats in which the changes of the brain ECS structure were reversed and found that the slowed DECS and ISF drainage persisted, confirming that the down-regulation of ISF drainage following neuronal excitation was mainly attributable to the release of neurotransmitters rather than to structural changes of the brain ECS. Meanwhile, the dynamic changes in the DECS were synchronized with the release and elimination processes of neurotransmitters following neuronal excitation. In conclusion, the downregulation of ISF drainage following neuronal excitation was found to be caused by the restricted diffusion in the brain ECS, and DECS mapping may be used to track the neuronal activity in the deep brain.

Highlights

The brain extracellular space (ECS) is a direct microscopic environment in which brain cells survive and function; it occupies 15–20% of the whole brain volume [1]
Dynamic changes in the ECS structure and interstitial fluid (ISF) drainage in thalamus after pain stimulation Our modified T1 magnetization-prepared rapid gradientecho scanning protocol allowed us to dynamically observe the ISF drainage of rats on the whole-brain scale, which increased the sensitivity to the changes in diffusion parameters in the brain ECS induced by the stimulus
The results showed that morphological changes in astrocytes following electrical stimulation were not found in the aquaporin-4 gene (AQP4)- and stimulation group (SG)-AQP4- groups, which further verified the results obtained by tracer-based magnetic resonance imaging (MRI) (Fig. 6A-C)

Summary

Introduction

The brain extracellular space (ECS) is a direct microscopic environment in which brain cells survive and function; it occupies 15–20% of the whole brain volume [1]. In the present study, using tracer-based MRI and effective diffusion coefficient (DECS)-mapping techniques, we quantitatively measured the dynamic biophysical parameters of the brain ECS structure and ISF drainage following neuronal excitation in the thalamus of electric pain stimulation rat model. The same examinations were performed in an AQP4 knockout rat model to explore the roles of AQP4 in regulating ECS structure and ISF drainage These data should allow us to delineate the mechanism by which neural networks interact with the ECS following neuronal excitation, providing new insights to elucidate the processing of perceptual information in the brain

Methods

Results

Conclusion