Role of NETosis in Central Nervous System Injury.

Yituo Chen,Kailiang Zhou,Wanta Cai,Xinli Hu,Wenfei Ni,Haojie Zhang

doi:10.1155/2022/3235524

Abstract

Central nervous system (CNS) injury is divided into brain injury and spinal cord injury and remains the most common cause of morbidity and mortality worldwide. Previous reviews have defined numerous inflammatory cells involved in this process. In the human body, neutrophils comprise the largest numbers of myeloid leukocytes. Activated neutrophils release extracellular web-like DNA amended with antimicrobial proteins called neutrophil extracellular traps (NETs). The formation of NETs was demonstrated as a new method of cell death called NETosis. As the first line of defence against injury, neutrophils mediate a variety of adverse reactions in the early stage, and we consider that NETs may be the prominent mediators of CNS injury. Therefore, exploring the specific role of NETs in CNS injury may help us shed some light on early changes in the disease. Simultaneously, we discovered that there is a link between NETosis and other cell death pathways by browsing other research, which is helpful for us to establish crossroads between known cell death pathways. Currently, there is a large amount of research concerning NETosis in various diseases, but the role of NETosis in CNS injury remains unknown. Therefore, this review will introduce the role of NETosis in CNS injury, including traumatic brain injury, cerebral ischaemia, CNS infection, Alzheimer's disease, and spinal cord injury, by describing the mechanism of NETosis, the evidence of NETosis in CNS injury, and the link between NETosis and other cell death pathways. Furthermore, we also discuss some agents that inhibit NETosis as therapies to alleviate the severity of CNS injury. NETosis may be a potential target for the treatment of CNS injury, so exploring NETosis provides a feasible therapeutic option for CNS injury in the future.

Highlights

Neutrophils, which originate from hematopoietic stem cells, account for almost 50-70% of all white blood cells
Further studies indicated that Ca2+ overload induced by A23187 leads to increased mitochondrial ROS generation, while mtROS is cause NETosis by activating NADPH oxidase and other pathways that do not involve NADPH oxidase, and mtROS is produced under the influence of the mitochondrial permeability transition pore (Figure 1) [15, 20, 24, 25]
The results show that high-mobility group box-1 (HMGB1) induces NETosis via TLR4 and CXCR4, which is consistent with the results described in the pretext that TLR4 is able to trigger the release of neutrophil extracellular traps (NETs) [82]

Summary

Introduction

Neutrophils, which originate from hematopoietic stem cells, account for almost 50-70% of all white blood cells. Once the host is infected by microorganisms, neutrophils immediately move from the bloodstream to the target of infection, serving as a “first line” of defence against foreign invaders Suicidal NETosis will cause cell death after the release of NETs, while cells remain alive in vital NETosis. These two different types of NETosis have their own functions and play an important role in immune defensive reactions. Damage of the CNS results in inflammatory responses from peripheral immune cells (such as T cells, monocytes, and neutrophils), macrophages, and resident microglia [6]. Many cells mediated by various pathways of cell death have been identified in injury diseases, but the role of NETosis by neutrophils in CNS trauma remains unclear. We summarize recent studies of NETosis in CNS trauma to provide a feasible future therapeutic method for CNS injury

Mechanism of NETosis

Linkage between NETosis and Other Cell Death Pathways

Evidence of NETosis in CNS Injury

Therapy Methods of NETosis

Conclusion

Conflicts of Interest