Neutrophil extracellular traps as a unique target in the treatment of chemotherapy-induced peripheral neuropathy

Wang, Chao-Yu; Lin, Tongtong; Hu, Liang; Xu, Chenjie; Fan, Hong-Yi; Li, Wan; Yang, Xing; Wu, Xuefeng; Zhang, Xiaotao; Li, Yan; Yin, Hao-Yuan; Jiang, Chun-Yi; Xin, Hongliang; Li, Wentao

doi:10.1016/j.ebiom.2023.104499

Cited by 25 publications

(8 citation statements)

References 43 publications

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“…Immunostaining analyses of 3D-transparized sciatic nerves allowed us to show that the global architecture of snBVs was not affected by acute oxaliplatin administration, although the mice exhibited robust neuropathic symptoms. So far, mouse models of acute OIPN have all been developed by single or repeated intraperitoneal injection(s) of oxaliplatin, which exclude to evaluate direct effect of oxaliplatin onto EC and mural cells of the vasa nervorum (Gauchan et al, 2009; Descoeur et al, 2011; Ogihara et al, 2019; Gould et al, 2021; Wang et al, 2023). Aiming at mimicking the patients’ oxaliplatin administration, we here investigated the relevance of a vascular component as the source of OIPN symptom initiation via intravenous injections of oxaliplatin.…”

Section: Discussionmentioning

confidence: 99%

Vascular dysfunction is at the onset of oxaliplatin-induced peripheral neuropathy symptoms in mice

Taib,

Durand,

Boulay

et al. 2024

Preprint

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Oxaliplatin-induced peripheral neuropathy (OIPN) is an adverse side effect of this chemotherapy used for gastrointestinal cancers. The continuous pain experienced by OIPN patients often result in the reduction or discontinuation of chemotherapy, thereby affecting patient survival. Several pathogenic mechanisms involving sensory neurons were shown to participate in the occurrence of OIPN symptoms. However, the dysfunction of the blood-nerve barrier as a source of nerve alteration had not been thoroughly explored. To characterise the vascular contribution to OIPN symptoms, we undertook two comparative transcriptomic analyses from mouse purified brain and sciatic nerve blood vessels (BVs), and nerve BVs after oxaliplatin or control administration. These analyses reveal distinct molecular landscapes between brain and nerve BVs and the upregulation of transcripts involved in vascular contraction after oxaliplatin treatment. Anatomical examination of the nerve yet shows the preservation of BV architecture in acute OIPN mouse model, although treated mice exhibit both neuropathic symptoms and enhanced vasoconstriction reflected by hypoxia. Moreover, vasodilators significantly reduce oxaliplatin-induced neuropathic symptoms and endoneurial hypoxia, establishing the key involvement of nerve blood flow in OIPN.

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Section: Discussionmentioning

confidence: 99%

Vascular dysfunction is at the onset of oxaliplatin-induced peripheral neuropathy symptoms in mice

Taib,

Durand,

Boulay

et al. 2024

Preprint

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“…Mpo is a gene encoding myeloperoxidase, which is most abundantly expressed in neutrophil granulocytes and often used as a quantitative indicator for neutrophil activity (Rizo-Tellez et al, 2022 ). Neutrophil infiltration in DRG has been reported in experimental autoimmune encephalomyelitis (EAE) model mice and in chemotherapy-induced peripheral neuropathy (CIPN) model mice (Harada et al, 2019 ; Wang et al, 2023 ). Neutrophils may contribute to the mechanical allodynia of these model mice by releasing elastase, forming neutrophil extracellular traps (NETs), or producing excessive oxidative stress (Zhang et al, 2019 ; Yin et al, 2020b ; Wang et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

“…Neutrophil infiltration in DRG has been reported in experimental autoimmune encephalomyelitis (EAE) model mice and in chemotherapy-induced peripheral neuropathy (CIPN) model mice (Harada et al, 2019 ; Wang et al, 2023 ). Neutrophils may contribute to the mechanical allodynia of these model mice by releasing elastase, forming neutrophil extracellular traps (NETs), or producing excessive oxidative stress (Zhang et al, 2019 ; Yin et al, 2020b ; Wang et al, 2023 ). These studies demonstrated the critical role of neutrophil infiltration in DRG in contributing to the pain mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Characterization of pain-related behaviors and gene expression profiling of peripheral sensory ganglia in a mouse model of acute ankle sprain

Pan

Yang

et al. 2023

Front. Behav. Neurosci.

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IntroductionLateral ankle sprain (LAS) is a very common type of joint injury. It occurred with high incidence among general population and especially among individuals participating sports and outdoor activities. A certain proportion of individuals who once developed LAS may suffer persistent ankle pain that affects daily activities. However, the mechanisms underlying LAS-induced pain still remained largely unknown.MethodsWe established a LAS mouse model and systematically evaluated the pain-related behaviors in this mouse model. RNA sequencing (RNA-Seq), combined with bioinformatics analysis, was undertaken to explore gene expression profiles. Immunostaining was used to study glial cell and neuron activation in ipsilateral spinal cord dorsal horn (SCDH) of LAS model mice. Ibuprofen was used to treat LAS model mice.ResultsThe LAS model mice developed obvious signs of mechanical and heat hypersensitivities as well as gait impairments in ipsilateral hind paws. Besides, LAS model mice developed signs of pain-related emotional disorder, including pain-induced aversion. By RNA-Seq, we were able to identify certain differentially expressed genes and signaling pathways that might contribute to pain mechanisms of LAS mouse model. In addition, LAS model mice showed increased c-Fos and p-ERK immunoreactivity as well as astrocyte and microglia overactivation in ipsilateral spinal cord dorsal horn, indicating central sensitization might occur. Finally, LAS model mice respond to ibuprofen, a drug clinically used to treat ankle sprain pain.ConclusionOur study found LAS model mice may be used as a preclinical animal model for screening novel targets or therapies for ankle sprain. Thus, the study may further help to understand molecular mechanisms contributing to ankle sprain-induced pain.

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“…Due to their reticular structure, NETs can capture a variety of cytokines, thereby contributing to the development of tumor drug resistance. Wang et al 104 found that during chemotherapy, the content of NETs in the blood continued to rise, and accumulated to capture tissue factors near peripheral nerves, induce the formation of thrombus and induce the expression of MMP9, resulting in pain in mice. It was found that in breast cancer cells after chemotherapy, NETs capture and activate the related protein TGF‐β, and MMP9, in turn, converts TGF‐β into the active form, inducing the occurrence of EMT in cancer cells, and ultimately developing chemotherapy resistance 83 …”

Section: Nets Regulatory Effects In the Tmementioning

confidence: 99%

Regulation of neutrophil extracellular traps in cancer

Xia,

Zhang,

Huang

et al. 2023

Intl Journal of Cancer

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Neutrophil extracellular trap (NET) is one of the defense functions of neutrophils, which has a rapid ability to kill infections and is also crucial in a variety of immune‐associated diseases including infections, tumors and autoimmune diseases. Recent studies have shown that NETs are closely related to the development of tumors. The regulatory role of NETs in tumors has been of interest to researchers. In addition to awakening latent tumor cells, NETs can also promote the proliferation and development of tumor cells and their metastasis to other sites. At the same time, NETs also have the effect of inhibiting tumors. At present, there are some new advances in the impact of NETs on tumor development, which will provide a more theoretical basis for developing NET‐targeted drugs. Therefore, this review just summarized the formation process of NETs, the regulation of tumor development and the treatment methods based on NETs.

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Neutrophil extracellular traps as a unique target in the treatment of chemotherapy-induced peripheral neuropathy

Cited by 25 publications

References 43 publications

Vascular dysfunction is at the onset of oxaliplatin-induced peripheral neuropathy symptoms in mice

Vascular dysfunction is at the onset of oxaliplatin-induced peripheral neuropathy symptoms in mice

Characterization of pain-related behaviors and gene expression profiling of peripheral sensory ganglia in a mouse model of acute ankle sprain

Regulation of neutrophil extracellular traps in cancer

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