Polydatin alleviates severe traumatic brain injury induced acute lung injury by inhibiting S100B mediated NETs formation

Gu, Zhengtao; Li, Li; Li, Qin; Tan, Hongping; Zou, Zhimin; Chen, Xueyong; Zhang, Zichen; Zhou, Yijun; Wei, Danian; Liu, Chengyong; Huang, Qiaobing; Maegele, Marc; Cai, Daozhang; Huang, Mengyi

doi:10.1016/j.intimp.2021.107699

Cited by 15 publications

(16 citation statements)

References 34 publications

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“…The third experiment to clarify whether PD has a protective effect on TBI second brain injury, rats were randomized into the sham group, the TBI group, and the TBI+ PD group, PD (5) (30 mg/kg; Haiwang, Shenzhen, China) was intraperitoneally injected immediately after TBI (n = 6 per group). The general pathological changes of the brain were observed by detection of brain histology at 6 h after TBI.…”

Section: Methodsmentioning

confidence: 99%

“…Astrocytes make up approximately 30% to 40% of the cells in the central nervous system and are an important part of the blood-brain barrier, establishing a large number of interactions with other cells in the central nervous system, including neurons. More importantly, secondary brain injury results in the loss of substantial neurocyte damage in the affected brain parenchyma (3,4), as well as damage to distant organs, such as lung, intestine, and liver injury (5)(6)(7). Therefore, it is necessary to explore the specific and deep mechanisms of neuroinflammation to block the inflammatory cascade and then alleviate TBI secondary brain injury.…”

Section: Introductionmentioning

confidence: 99%

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Polydatin ameliorates TBI induced secondary brain injury by inhibiting NLRP3-induced neuroinflammation associated with SOD2 acetylation

Zhao

et al. 2022

Shock

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Traumatic brain injury (TBI) is a kind of disease with high morbidity, mortality, and disability, and its pathogenesis is still unclear. Research shows that nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) activation in neurons and astrocytes is involved in neuroinflammatory cascades after TBI. What is more, polydatin (PD) has been shown to have a protective effect on TBI-induced neuroinflammation, but the mechanisms remain unclear. Here, we speculated that PD could alleviate TBI-induced neuroinflammatory damage through the superoxide dismutase (SOD2)-NLRP3 signal pathway, and SOD2 might regulate NLRP3 inflammasome activation. The model of lateral fluid percussion for in vivo and cell stretching injury for in vitro were established to mimic TBI. NLRP3 chemical inhibitor MCC950, SOD2 inhibitor 2-methoxyestradiol, and PD were administered immediately after TBI. As a result, the expression of SOD2 acetylation (SOD2 Ac-K122), NLRP3, and cleaved caspase-1 were increased after TBI both in vivo and in vitro, and using SOD2 inhibitor 2-methoxyestradiol significantly promoted SOD2 Ac-K122, NLRP3, and cleaved caspase-1 expression, as well as exacerbated mitochondrial ROS (mtROS) accumulation and mitochondrial membrane potential (MMP) collapse in PC12 cells. However, using NLRP3 inhibitor MCC950 significantly inhibited cleaved caspase-1 activation after TBI both in vivo and in vitro; meanwhile, MCC950 inhibited mtROS accumulation and MMP collapse after TBI. More importantly, PD could inhibit the level of SOD2 Ac-K122, NLRP3, and cleaved caspase-1 and promote the expression of SOD2 after TBI both in vivo and in vitro. Polydatin also inhibited mtROS accumulation and MMP collapse after stretching injury. These results indicated that PD inhibited SOD2 acetylation to alleviate NLRP3 inflammasome activation, thus acting a protective role against TBI neuroinflammation.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polydatin ameliorates TBI induced secondary brain injury by inhibiting NLRP3-induced neuroinflammation associated with SOD2 acetylation

Zhao

et al. 2022

Shock

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“…TBI-induced acute lung injury (TBI-induced ALI) is regarded as the most common complication of severe TBI that is an independent predictor of poor outcomes in TBI patients and strongly increases the mortality [40]. Concurred with those seen in other studies [41,42], our previous study has shown that TBI-induced activation of S100B could mediated the development of neutrophil extracellular traps (NETs) in the lung, leading to subsequent ALI [43]. Present study provides more evidence to reveal that S100B/RAGE and ADAM17 activation triggered the shedding of pulmonary endothelial glycocalyx and this change could be rescued with inhibitors targeting this pathway, suggesting that S100B/RAGE/ADAM17 is not only a key signal of astrocyte and endothelial cell damage, but also an important participant in local or systemic secondary injury after TBI.…”

Section: The S100b/rage-adma17-induced Eg Damage Is Involved In Prima...mentioning

confidence: 96%

The role of S100B/RAGE-enhanced ADAM17 activation in endothelial glycocalyx shedding after traumatic brain injury

Zou

et al. 2022

J Neuroinflammation

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Background Traumatic brain injury (TBI) remains one of the main causes for disability and death worldwide. While the primary mechanical injury cannot be avoided, the prevention of secondary injury is the focus of TBI research. Present study aimed to elucidate the effects and mechanisms of S100B and its receptor RAGE on mediating secondary injury after TBI. Methods This study established TBI animal model by fluid percussion injury in rats, cell model by stretch-injured in astrocytes, and endothelial injury model with conditioned medium stimulation. Pharmacological intervention was applied to interfere the activities of S100B/RAGE/ADAM17 signaling pathway, respectively. The expressions or contents of S100B, RAGE, syndecan-1 and ADAM17 in brain and serum, as well as in cultured cells and medium, were detected by western blot. The distribution of relative molecules was observed with immunofluorescence. Results We found that TBI could activate the release of S100B, mostly from astrocytes, and S100B and RAGE could mutually regulate their expression and activation. Most importantly, present study revealed an obvious increase of syndecan-1 in rat serum or in endothelial cultured medium after injury, and a significant decrease in tissue and in cultured endothelial cells, indicating TBI-induced shedding of endothelial glycocalyx. The data further proved that the activation of S100B/RAGE signaling could promote the shedding of endothelial glycocalyx by enhancing the expression, translocation and activity of ADAM17, an important sheddase, in endothelial cells. The damage of endothelial glycocalyx consequently aggravated blood brain barrier (BBB) dysfunction and systemic vascular hyper-permeability, overall resulting in secondary brain and lung injury. Conclusions TBI triggers the activation of S100B/RAGE signal pathway. The regulation S100B/RAGE on ADAM17 expression, translocation and activation further promotes the shedding of endothelial glycocalyx, aggravates the dysfunction of BBB, and increases the vascular permeability, leading to secondary brain and lung injury. Present study may open a new corridor for the more in-depth understanding of the molecular processes responsible for cerebral and systemic vascular barrier impairment and secondary injury after TBI.

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“…In addition, the S100B inhibitor polydatin has been shown to have a therapeutic effect in severe TBI, both on TBI-induced neuronal damage and secondary lung injury. By inhibiting S100B expression, this molecule promotes lung vascular permeability recovery and attenuates the oxidative stress response and inflammatory cytokines release [ 139 ]. Papaverine may be another potential therapeutic target for acute TBI, potentially via the RAGE-NF-κB signaling pathway and by possibly inhibiting microglia activation.…”

Section: S100b As a Putative Therapeutic Targetmentioning

confidence: 99%

S100B, Actor and Biomarker of Mild Traumatic Brain Injury

Oris

Kahouadji

Durif³

et al. 2023

IJMS

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Mild traumatic brain injury (mTBI) accounts for approximately 80% of all TBI cases and is a growing source of morbidity and mortality worldwide. To improve the management of children and adults with mTBI, a series of candidate biomarkers have been investigated in recent years. In this context, the measurement of blood biomarkers in the acute phase after a traumatic event helps reduce unnecessary CT scans and hospitalizations. In athletes, improved management of sports-related concussions is also sought to ensure athletes’ safety. S100B protein has emerged as the most widely studied and used biomarker for clinical decision making in patients with mTBI. In addition to its use as a diagnostic biomarker, S100B plays an active role in the molecular pathogenic processes accompanying acute brain injury. This review describes S100B protein as a diagnostic tool as well as a potential therapeutic target in patients with mTBI.

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Polydatin alleviates severe traumatic brain injury induced acute lung injury by inhibiting S100B mediated NETs formation

Cited by 15 publications

References 34 publications

Polydatin ameliorates TBI induced secondary brain injury by inhibiting NLRP3-induced neuroinflammation associated with SOD2 acetylation

Polydatin ameliorates TBI induced secondary brain injury by inhibiting NLRP3-induced neuroinflammation associated with SOD2 acetylation

The role of S100B/RAGE-enhanced ADAM17 activation in endothelial glycocalyx shedding after traumatic brain injury

S100B, Actor and Biomarker of Mild Traumatic Brain Injury

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