VX-765 reduces neuroinflammation after spinal cord injury in mice

Chen, Jing; Chen, Yuqing; Shi, Yujiao; Ding, Songtao; Shen, Lin; Wang, Rui; Wang, Qiyi; Zha, Cheng; Ding, Hengfei; Hu, Jianguo; Lü, He‐Zuo

doi:10.4103/1673-5374.306096

Cited by 26 publications

(7 citation statements)

References 65 publications

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“…Tregs are involved in maintaining immune homeostasis and suppressing neuroinflammation in the pathophysiological conditions affecting the CNS 45 . Previous studies have reported that increasing Treg population promoted locomotor recovery after SCI 24–26 . However, whether and how Tregs regulate the injured microenvironment after SCI has remained largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“… 45 Previous studies have reported that increasing Treg population promoted locomotor recovery after SCI. 24 , 25 , 26 However, whether and how Tregs regulate the injured microenvironment after SCI has remained largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…The immunoregulatory effects of Tregs on microglia were further supported by in vitro studies where Tregs, through secretion of anti‐inflammatory cytokines (IL‐10, IL‐35, TGF‐β), were shown to directly suppress the production of proinflammatory cytokines and chemokines by cultured microglia 22,23 . Previous studies have reported that treatment with IL‐10, VX‐765, or CCL28 increases Treg numbers and reinforces functional recovery after SCI 24–26 . However, whether and how Tregs interact with microglia and modulate injured microenvironment after SCI remains unknown.…”

Section: Introductionmentioning

confidence: 96%

“… 22 , 23 Previous studies have reported that treatment with IL‐10, VX‐765, or CCL28 increases Treg numbers and reinforces functional recovery after SCI. 24 , 25 , 26 However, whether and how Tregs interact with microglia and modulate injured microenvironment after SCI remains unknown. Recent studies have revealed that Tregs suppress the IL‐6–STAT3 signaling pathway in a mouse model of middle cerebral artery occlusion.…”

Section: Introductionmentioning

confidence: 99%

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Regulatory T cells promote functional recovery after spinal cord injury by alleviating microglia inflammation via STAT3 inhibition

Liu

Wang

et al. 2023

CNS Neurosci Ther

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Spinal cord injury (SCI) often leads to permanent paraplegia; therefore, it represents a major global health priority. 1,2 Immediately following a spinal trauma, the breakdown of the blood-spinal cord barrier causes an influx of immune cells and proinflammatory cytokines, such as TNFα and IL-1β, into the spinal cord, which triggers an inflammatory cascade. 3 This inflammation eventually unbalances

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Regulatory T cells promote functional recovery after spinal cord injury by alleviating microglia inflammation via STAT3 inhibition

Liu

Wang

et al. 2023

CNS Neurosci Ther

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“…Chen et al. demonstrated that VX-765 reduced neuroinflammation in an SCI mouse model by inhibiting caspase-1/IL-1β/IL-18 ( 126 ).…”

Section: Inhibiting the Inflammasome Pathwaysmentioning

confidence: 99%

An emerging role of inflammasomes in spinal cord injury and spinal cord tumor

Chen

Shen²,

Shao³

et al. 2023

Front. Immunol.

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Spinal cord injury (SCI) and spinal cord tumor are devastating events causing structural and functional impairment of the spinal cord and resulting in high morbidity and mortality; these lead to a psychological burden and financial pressure on the patient. These spinal cord damages likely disrupt sensory, motor, and autonomic functions. Unfortunately, the optimal treatment of and spinal cord tumors is limited, and the molecular mechanisms underlying these disorders are unclear. The role of the inflammasome in neuroinflammation in diverse diseases is becoming increasingly important. The inflammasome is an intracellular multiprotein complex and participates in the activation of caspase-1 and the secretion of pro-inflammatory cytokines such as interleukin (IL)-1β and IL-18. The inflammasome in the spinal cord is involved in the stimulation of immune-inflammatory responses through the release of pro-inflammatory cytokines, thereby mediating further spinal cord damage. In this review, we highlight the role of inflammasomes in SCI and spinal cord tumors. Targeting inflammasomes is a promising therapeutic strategy for the treatment of SCI and spinal cord tumors.

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VX‐765 alleviates motor and cognitive impairments via inhibiting PANoptosis activation in the neonatal rats after hypoxic–ischemic brain damage

Li,

Chen,

et al. 2024

Pediatric Discovery

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Neonatal hypoxia–ischemia (HI) is one of the main factors that cause neonatal severe neurologic impairment and death. Shown by a large number of studies, caspase‐1 plays a significant effect in diseases such as hypoxic–ischemic brain damage (HIBD) and may be a key component of the protein complex that initiates PANoptosis. VX‐765, an inhibitor of caspase‐1, exerts a potential neuroprotective effect in traumatic brain injury. However, it is unknown whether the administration of VX‐765 has neuroprotective effects on neonatal rats that suffered HIBD, and if so, the underlying mechanisms are also still unknown. In the present study, we found that treatment with VX‐765 (50 mg/kg, i.p.) significantly ameliorated the impairment of locomotor coordination functions and myodynamia as well as the spatial learning and memory in neonatal rats subjected with HIBD. These behavior improvements were attributed to VX‐765 reducing infarct volumes and neuronal loss in the CA1, CA3 region of hippocampus, and deeper layers of the cortex in HIBD rats. Moreover, the enzyme‐linked immunosorbent assay showed that VX‐765 obviously decreased the production of neuroinflammatory factors including TNF‐α, IL‐1β, and IL‐6. Importantly, we identified HI promoted PANoptosis activation in vivo and in vitro, and VX‐765 obviously suppressed PANoptosis activation. Finally, we demonstrated that VX‐765 treatment reversed neuronal injury induced by oxygen–glucose deprivation (OGD). Taken together, these results suggest that VX‐765 protects the neurons against damage by suppressing neuroinflammation and PANoptosis activation, thereby improving locomotor coordination and cognitive impairments in neonatal HIBD rats, indicating that VX‐765 may be an underlying therapeutic drug for the clinical treatment of hypoxic–ischemic encephalopathy (HIE).

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VX-765 reduces neuroinflammation after spinal cord injury in mice

Cited by 26 publications

References 65 publications

Regulatory T cells promote functional recovery after spinal cord injury by alleviating microglia inflammation via STAT3 inhibition

Regulatory T cells promote functional recovery after spinal cord injury by alleviating microglia inflammation via STAT3 inhibition

An emerging role of inflammasomes in spinal cord injury and spinal cord tumor

VX‐765 alleviates motor and cognitive impairments via inhibiting PANoptosis activation in the neonatal rats after hypoxic–ischemic brain damage

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