The Involvement of Aquaporin-4 in the Interstitial Fluid Drainage Impairment Following Subarachnoid Hemorrhage.

E Liu,Xiaomei Yang,Xianlong Peng,Linlin Sun,Haowen Ma,Yan Zhang,Yixuan Zhang,Junhao Yan

doi:10.3389/fnagi.2020.611494

Abstract

The mechanism of brain injury following subarachnoid hemorrhage (SAH) has not yet been clarified. The glymphatic system (GS), a glia-dependent waste clearance pathway, drains away soluble waste proteins and metabolic products, even some toxic factors from the brain. Aquaporin-4 (Aqp4) is highly expressed on the astrocyte foot processes and facilitates the interstitial fluid (ISF) transportation in the GS system. In this study, the role of Aqp4 in the GS injury after SAH was explored using Aqp4 gene knockout (Aqp4−/−) Sprague Dawley rats. The results of MRI, fluorescent imaging, and transmission electron microscopy (TEM) indicated that, after SAH, the inflow of cerebrospinal fluid (CSF) into the brain and the clearance of ISF from the brain were both significantly decreased. Meanwhile, the expression level of Aqp4 around the artery was markedly higher than that around the vein following SAH. Aqp4 knockout exacerbated the GS damage after SAH. In summary, after SAH, there was an apparent GS impairment, and Aqp4 played key roles in modulating the function of GS in the brain.

Highlights

Subarachnoid hemorrhage (SAH) is mainly caused by the rupture of intracranial aneurysms, and the fatality rate is about 40% (Macdonald et al, 2007)
The results indicated that the expression level of Aqp4 in the hippocampus was markedly decreased in the Aqp4−/−-sham and Aqp4−/−-SAH groups, and interestingly, the expression level of Aqp4 was significantly increased in the SAH group (p < 0.05, Figure 1C)
The results of MRI, fluorescence imaging, and transmission electron microscopy (TEM) examination revealed that the glymphatic system (GS) in the brain was impaired after SAH, which could be aggravated after Aqp4 deletion

Summary

Introduction

Subarachnoid hemorrhage (SAH) is mainly caused by the rupture of intracranial aneurysms, and the fatality rate is about 40% (Macdonald et al, 2007). It is reported that EBI is a determining factor for the poor outcomes after SAH (Sehba et al, 2012). The previous studies about SAH were mainly focused on neuronal apoptosis, BBB disruption, inflammation, and oxidative stress (Gleichman and Carmichael, 2014; Sehba, 2015); until now, no significant breakthrough has been achieved.

Methods

Results

Conclusion