NETs Lead to Sympathetic Hyperactivity After Traumatic Brain Injury Through the LL37-Hippo/MST1 Pathway

Zhu, Kaixin; Zhu, Yibai; Hou, Xi; Chen, Wen; Qu, Xiaolin; Zhang, Yelei; Liu, Zhenxing; Wang, Chunhui; Chen, Jigang; Lv, Liquan; Wang, Junyu; Zhang, Danfeng; Hou, Lingling

doi:10.3389/fnins.2021.621477

Cited by 18 publications

(23 citation statements)

References 39 publications

(57 reference statements)

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“…Study shows that after TBI, the levels of normetanephrine and metanephrine initially increased at 9 h and reached their highest values at 72 h [ 68 ]. After injury, in the paraventricular nucleus (PVN), a continuous increase in the concentration of NETs was observed at 24 and 72 h [ 68 – 71 ]. A positive connection between blood catecholamine and PVN or NET levels was found [ 68 – 71 ].…”

Section: Evidence Of Netosis In Cns Injurymentioning

confidence: 99%

“…After injury, in the paraventricular nucleus (PVN), a continuous increase in the concentration of NETs was observed at 24 and 72 h [ 68 – 71 ]. A positive connection between blood catecholamine and PVN or NET levels was found [ 68 – 71 ]. The flow cytometry assay of peripheral blood cells demonstrated that compared with the control group, there was a much higher level of NETs in the injury group [ 68 – 71 ].…”

Section: Evidence Of Netosis In Cns Injurymentioning

confidence: 99%

“…A positive connection between blood catecholamine and PVN or NET levels was found [ 68 – 71 ]. The flow cytometry assay of peripheral blood cells demonstrated that compared with the control group, there was a much higher level of NETs in the injury group [ 68 – 71 ]. The immunofluorescence results proved that NETs appeared in the PVN after TBI, the positive immunoprecipitation results indicated that LL37 was correlated with P2 × 7 [ 68 – 71 ].…”

Section: Evidence Of Netosis In Cns Injurymentioning

confidence: 99%

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Role of NETosis in Central Nervous System Injury

Chen

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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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.

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Section: Evidence Of Netosis In Cns Injurymentioning

confidence: 99%

Section: Evidence Of Netosis In Cns Injurymentioning

confidence: 99%

Section: Evidence Of Netosis In Cns Injurymentioning

confidence: 99%

See 1 more Smart Citation

Role of NETosis in Central Nervous System Injury

Chen

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The researchers revealed that the formation of NETs was induced by the activation of TLR4 via a PAD4-dependent mechanism and then resulted in neurological deficits (61). In 2021, researchers have demonstrated the presence of NETs in paraventricular nucleus (PVN) after TBI and NETs activated microglia dependent on the LL37-Hippo/ MST1 pathway to facilitate the IL-1b release, which may lead to the occurrence of sympathetic excitation as a result (62). Oggioni et al reported the presence of PTX3 in the mouse brain parenchyma, next to astrocytes, neurons, microglia, and endothelial cells, in the subacute phase of TBI for the first time (63).…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Role of the Extracellular Traps in Central Nervous System

Zeng

Cai

et al. 2021

Front. Immunol.

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It has been reported that several immune cells can release chromatin and granular proteins into extracellular space in response to the stimulation, forming extracellular traps (ETs). The cells involved in the extracellular trap formation are recognized including neutropils, macrophages, basophils, eosinophils, and mast cells. With the development of research related to central nervous system, the role of ETs has been valued in neuroinflammation, blood–brain barrier, and other fields. Meanwhile, it has been found that microglial cells as the resident immune cells of the central nervous system can also release ETs, updating the original understanding. This review aims to clarify the role of the ETs in the central nervous system, especially in neuroinflammation and blood–brain barrier.

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“…Zhu et al documented that NETs activation in the paraventricular nucleus is connected with sympathetic hyperactivity after traumatic brain damage. In animal model authors observed that reactive oxygen species in the paraventricular nucleus activate formation and chemotaxis of NETs which finally relate to the activation of microglia cells and increased secretion of IL-1β via the hippo/MST1 pathway [16].…”

Section: Neutrophils In Tbimentioning

confidence: 99%

Credibility of the Neutrophil-to-Lymphocyte Count Ratio in Severe Traumatic Brain Injury

Siwicka-Gieroba

Dąbrowski

2021

Life

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Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality worldwide. The consequences of a TBI generate the activation and accumulation of inflammatory cells. The peak number of neutrophils entering into an injured brain is observed after 24 h; however, cells infiltrate within 5 min of closed brain injury. Neutrophils release toxic molecules including free radicals, proinflammatory cytokines, and proteases that advance secondary damage. Regulatory T cells impair T cell infiltration into the central nervous system and elevate reactive astrogliosis and interferon-γ gene expression, probably inducing the process of healing. Therefore, the neutrophil-to-lymphocyte ratio (NLR) may be a low-cost, objective, and available predictor of inflammation as well as a marker of secondary injury associated with neutrophil activation. Recent studies have documented that an NLR value on admission might be effective for predicting outcome and mortality in severe brain injury patients.

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NETs Lead to Sympathetic Hyperactivity After Traumatic Brain Injury Through the LL37-Hippo/MST1 Pathway

Cited by 18 publications

References 39 publications

Role of NETosis in Central Nervous System Injury

Role of NETosis in Central Nervous System Injury

Role of the Extracellular Traps in Central Nervous System

Credibility of the Neutrophil-to-Lymphocyte Count Ratio in Severe Traumatic Brain Injury

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