Regulating effect of activated NF-κB on edema induced by traumatic brain injury of rats

Wang, Zi-Ran; Li, Yuxin; Lei, Hongyan; Yang, Dai-Qun; Wang, Liquan; Luo, Mingyu

doi:10.1016/j.apjtm.2016.01.027

Cited by 13 publications

(10 citation statements)

References 17 publications

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“…First, it has been shown to be involved in the pathogenesis of TBI. 38,39 Second, NF-jB/p65 is a wellestablished priming signal for NLRP3 inflammasomes. 40 Transcriptional priming of inflammasome constituents like caspase-1 is an essential prerequisite step for further NLRP3 inflammasome activation and subsequent IL-1b maturation.…”

Section: Discussionmentioning

confidence: 99%

MCC950, the Selective Inhibitor of Nucleotide Oligomerization Domain-Like Receptor Protein-3 Inflammasome, Protects Mice against Traumatic Brain Injury

Ismael

Nasoohi

Ishrat

2018

Journal of Neurotrauma

150

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Nucleotide oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome may intimately contribute to sustaining damage after traumatic brain injury (TBI). This study aims to examine whether specific modulation of NLPR3 inflammasome by MCC950, a novel selective NLRP3 inhibitor, confers protection after experimental TBI. Unilateral cortical impact injury was induced in young adult C57BL/6 mice. MCC950 (50 mg/kg, intraperitoneally) or saline was administration at 1 and 3 h post-TBI. Animals were tested for neurological function and then sacrificed at 24 or 72 h post-TBI. Immunoblotting and histological analysis were performed to identify markers of NLRP3 inflammasome and proapoptotic activity in pericontusional areas of the brains at 24 or 72 h post-TBI. MCC950 treatment provided a significant improvement in neurological function and reduced cerebral edema in TBI animals. TBI upregulated NLRP3, apoptosis-associated speck-like adapter protein (ASC), cleaved caspase-1, and interlukein-1β (IL-1β) in the perilesional area. MCC950 efficiently repressed caspase-1 and IL-1β with a transient effect on ASC and NLRP3 post-TBI. MCC950 treatment also provided protection against proapoptotic activation of poly (ADP-ribose) polymerase and caspase-3 associated with TBI. A concurrent inhibition of inflammasome priming was also detectable at the nuclear factor kappa B/p65 and caspase-1 level. Our findings support the implication of NLRP3 inflammasome in the pathogenesis of TBI and further suggests the therapeutic potential of MCC950.

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Section: Discussionmentioning

confidence: 99%

MCC950, the Selective Inhibitor of Nucleotide Oligomerization Domain-Like Receptor Protein-3 Inflammasome, Protects Mice against Traumatic Brain Injury

Ismael

Nasoohi

Ishrat

2018

Journal of Neurotrauma

150

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“…In addition, a number of recent studies have found that pharmacological treatments that directly or indirectly target this inflammasome can reduce its activity following moderate-to-severe TBI. These treatments are broadly broken into four groups: (i) treatments derived from naturally occurring compounds (e.g., mangiferin [83], omega-3 fatty acids [71], and apocynin [84]); (ii) repurposed medications (e.g., propofol [85], and telmisartan [86]); (iii) inhibitors of NLRP3-associated molecules (e.g., ASC antibodies [87], NF-κB inhibitor, Bay 11-7082 [88][89][90][91]); and (iv) specific NLRP3 inflammasome inhibitors (e.g., MCC950 [69], JC-124 [92]). While the first three treatment categories have been shown to decrease NLRP3 inflammasome activity as well as demonstrating a neuroprotective effect, they do not target NLRP3 activation specifically.…”

Section: Nlrp3 As a Therapeutic Target For Tbimentioning

confidence: 99%

The NLRP3 inflammasome in traumatic brain injury: potential as a biomarker and therapeutic target

O’Brien

Pham

Symons

et al. 2020

J Neuroinflammation

158

108

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There is a great clinical need to identify the underlying mechanisms, as well as related biomarkers, and treatment targets, for traumatic brain injury (TBI). Neuroinflammation is a central pathophysiological feature of TBI. NLRP3 inflammasome activity is a necessary component of the innate immune response to tissue damage, and dysregulated inflammasome activity has been implicated in a number of neurological conditions. This paper introduces the NLRP3 inflammasome and its implication in the pathogenesis of neuroinflammatory-related conditions, with a particular focus on TBI. Although its role in TBI has only recently been identified, findings suggest that priming and activation of the NLRP3 inflammasome are upregulated following TBI. Moreover, recent studies utilizing specific NLRP3 inhibitors have provided further evidence that this inflammasome is a major driver of neuroinflammation and neurobehavioral disturbances following TBI. In addition, there is emerging evidence that circulating inflammasome-associated proteins may have utility as diagnostic biomarkers of neuroinflammatory conditions, including TBI. Finally, novel and promising areas of research will be highlighted, including the potential involvement of the NLRP3 inflammasome in mild TBI, how factors such as biological sex may affect NLRP3 activity in TBI, and the use of emerging biomarker platforms. Taken together, this review highlights the exciting potential of the NLRP3 inflammasome as a target for treatments and biomarkers that may ultimately be used to improve TBI management.

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“…NF-κB comprises a group of transcription factors in eukaryocytes, which is distributed widely in the nervous system (23). Under physiological conditions, it does not have transcriptional activities.…”

Section: Discussionmentioning

confidence: 99%

“…NF-κB and IκB are activated and shift into the nucleus from the cytoplasm (24). Studies have found that NF-κB is activated in rats with SCP at an early stage (23,25). Activated NF-κB can be found in the cytoplasm and cell nuclei of neurons 24 h following injury (25).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of tanshinone IIA weakens spastic cerebral palsy through inflammation, p38MAPK and VEGF in neonatal rats

et al. 2017

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As one of main active ingredients of salvia miltiorrhizae, which is a traditional Chinese medicine, tanshinone IIA is the basis of its pharmacological activities. In the present study, the effect of tanshinone IIA on weakening spastic cerebral palsy (SCP) in neonatal rats was investigated. Radial arm water maze and holding tests were used to measure the alterations of spastic cerebral palsy, inflammation was measured using an ELISA kit, and western blot analysis was used to analyze the protein expression of p‑p38 mitogen‑activated protein kinase (MAPK) and vascular endothelial growth factor (VEGF). The central mechanisms involved in the mediation or modulation of inflammation, p‑p38 MAPK and VEGF were also investigated. Treatment with tanshinone IIA effectively inhibited spastic cerebral palsy, and the activities of interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α, monocyte chemoattractant protein 1, cyclooxygenase‑2 and prostaglandin E2 in a neonatal rat model of SCP. Tanshinone IIA effectively suppressed the protein expression of inducible nitric oxide synthase (NOS), phosphorylated (p‑) nuclear factor (NF)‑κB, p‑p38MAPK and VEGF, and activated the phosphorylation of inhibitor of NF‑κB and the protein expression of neuronal NOS in the SCP rat model. These results suggested that the neuroprotective effect of tanshinone IIA weakened SCP through inflammation, p38MAPK and VEGF in the neonatal rats.

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Regulating effect of activated NF-κB on edema induced by traumatic brain injury of rats

Abstract: The results show that the activation of NF-κB in astrocytes is a key factor in the process of cerebral edema after TBI of rats.

Cited by 13 publications

References 17 publications

MCC950, the Selective Inhibitor of Nucleotide Oligomerization Domain-Like Receptor Protein-3 Inflammasome, Protects Mice against Traumatic Brain Injury

MCC950, the Selective Inhibitor of Nucleotide Oligomerization Domain-Like Receptor Protein-3 Inflammasome, Protects Mice against Traumatic Brain Injury

The NLRP3 inflammasome in traumatic brain injury: potential as a biomarker and therapeutic target

Neuroprotective effect of tanshinone IIA weakens spastic cerebral palsy through inflammation, p38MAPK and VEGF in neonatal rats

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