MiR-7-5p Affects Brain Edema After Intracerebral Hemorrhage and Its Possible Mechanism.

Xiqian Chen,Jingjing Nie,Wei Lu,Shuwen Deng,Qiang He,Qiang Lei,Yijun Ren,Yiliu Zhang

doi:10.3389/fcell.2020.598020

Abstract

Objective: To explore the relationship between miR-7-5p and brain edema after intracerebral hemorrhage and the role of butylphthalide (NBP) in brain edema after intracerebral hemorrhage.Method: Routine blood testing, C-reactive protein results, and computed tomography data were collected 1, 7, and 14 days after intracerebral hemorrhage in six patients. Levels of MMP-9, ZO-1, occludin, IL-6, TNF-α, and miR-7-5p were detected in each patient's serum. Sixty male Sprague–Dawley rats were randomly divided into sham operation, intracerebral hemorrhage, and NBP treatment groups. Dry–wet weight was used to assess brain edema, and Evans blue staining was used to assess the permeability of the blood–brain barrier. Expression levels of IL-6, TNF-α, ZO-1 and occludin, PI3K, AKT, p-AKT, AQP4, and miR-7-5p were analyzed in the rat brains.Result: The blood neutrophil–lymphocyte ratio (NLR) on day 1 was associated with the area of brain edema on day 7. The expression of miR-7-5p decreased after intracerebral hemorrhage, and as a result, the inhibition of the PI3K/AKT pathway was weakened. The decreased inhibition of the PI3K/AKT pathway resulted in an increase in AQP4 expression, which further aggravated brain edema. NBP can upregulate the expression of miR-7-5p, affecting these pathways to reduce brain edema.Conclusion: After intracerebral hemorrhage, miR-7-5p expression in brain tissue is reduced, which may increase the expression of AQP4 by activating the PI3K/AKT pathway. NBP can inhibit this process and reduce brain edema.

Highlights

Intracerebral hemorrhage (ICH) is an important cause of disability and death in the elderly
Previous studies have found that miR-7-5p affects PI3K/AKT pathway activity, and PI3K/AKT pathway regulates AQP4 expression, but there have been no studies exploring the relationship between miR-75p and AQP4
This study aimed to explore whether miR-7-5p can affect AQP4 expression after ICH through the PI3K/AKT pathway and to explore whether these processes affect the development of brain edema after ICH

Summary

Introduction

Intracerebral hemorrhage (ICH) is an important cause of disability and death in the elderly. The formation of brain edema plays an important role in the neurological deficit caused by ICH. A large number of studies have shown that elevated AQP4 expression is the main cause of brain edema caused by brain injury (Lo Pizzo et al, 2013; Khalaf et al, 2018; Glober et al, 2019; Zhang Y. et al, 2019; Clement et al, 2020). There have been several studies that found that AQP4 expression may be regulated by the PI3K/AKT signaling pathway (Kapoor et al, 2013; Chu et al, 2017; Zhao et al, 2017; Song et al, 2018). A study has found that a microRNA, miR-7-5p, can affect the activity of the PI3K/AKT pathway (Shukla et al, 2018)

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