Mast Cell Deficiency Protects Mice from Surgery-Induced Neuroinflammation.

Xiang Zhang,Jun Zhang,Hongquan Dong,Fei Wang

doi:10.1155/2020/1921826

Abstract

Neuroinflammation plays a key role in the occurrence and development of neurodegenerative diseases. Microglia, the resident immune cells in the brain, have been recognized to contribute to neuroinflammation. Previous studies have shown that activated mast cells may be involved in surgery-induced neuroinflammation and neuronal apoptosis by using pharmacological methods. This study is aimed at ascertaining the exactly role of mast cells on neuroinflammation with the mast cell-deficient mice. Adult male C57BL6/J wild-type (WT) and mast cell-deficient (C57BL6/J KitWsh/Wsh (Wsh)) mice underwent tibial fracture surgery. Blood-brain barrier (BBB) breakdown, microglial activation, and neuroinflammatory levels were examined at 1 day after surgery. Surgery-induced BBB breakdown, microglial activation, and neuroinflammatory levels were significantly, pharmacologically reduced using a mast cell stabilizer, cromolyn sodium in WT mice (P < 0.05). These results were reproduced with mast cell deficiency. WT mice administered intraventricularly with cromolyn exhibited reduced BBB breakdown, microglial activation, and neuroinflammatory levels versus vehicle (P < 0.05). But there was no effect of cromolyn versus vehicle in Wsh mice, clarifying the specificity of cromolyn on brain mast cells. These findings demonstrated that activated mast cells promote surgery-induced BBB breakdown and neuroinflammation in mice, and open up a new therapeutic target for neuroinflammation-related diseases.

Highlights

It is widely recognized that neuroinflammation plays an important role in CNS disorders, such as neurodegenerative diseases [1]
A notable microglial activation in the hippocampus was induced by surgery (Figure 1(b))
As the same results with our previous studies, surgery induced the obvious increase of tumor necrosis factor-α (TNF-α) and IL-1β (Figure 1(c))

Summary

Introduction

It is widely recognized that neuroinflammation plays an important role in CNS disorders, such as neurodegenerative diseases [1]. The induction and acceleration of neuroinflammation seem to depend on the communication between microglia, neurons, and immune cells. Little is known about the microglial immune cell connection far. Animal models of peripheral surgical intervention, such as tibial fracture, trigger neuroinflammation in the brain, which is frequently used as an animal model for studying neurodegeneration [2]. Microglia are primary resident immune cells in the brain. Accumulating reports have defined microglial activation as an important element of neuroinflammation. Microglia could be classified into two states: a M1 reactive phenotype initiating an inflammatory response and M2 phenotype with an anti-inflammatory role. Overactivation of microglia produces numerous inflammatory mediators, leading to neuronal damage and brain injury. Restraining microglia-induced excessive inflammatory response may improve neurodegenerative diseases

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