Abstract:
OBJECTIVE:High-mobility group box 1 (HMGB1) was shown to be a major extracellular mediator involved in relayed neuro-inflammation in animals after subarachnoid hemorrhage (SAH). It is of interest to examine the effect of rhinacanthin-C (RCT-C, C25H30O5) on pro-inflammatory cytokines/HMGB1 in an SAH-related early brain injury model. METHODS:A rodent double SAH model was used. RCT-C was administered orally at 100, 200, and 400 μmol/kg/day. Cerebral spinal fluid samples were obtained to assess interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α using a real-time polymerase chain reaction. Basilar arteries were harvested and cerebral cortex was examined for HMGB1 mRNA and protein expression (western blot) and caspases (real-time polymerase chain reaction). An intrathecal injection of 1 ng of HMGB-1 recombinant protein was given in the 400 μmol/kg/day RCT-C plus SAH groups. RESULTS:The levels of IL-1β, IL-6, and tumor necrosis factor α mRNA were significantly increased in animals subject to SAH, compared with the healthy controls, but were absent in the RCT-C groups. Cleaved caspase-9a as well as HMGB-1 mRNA and protein were significantly reduced in the 400 μmol/kg/day RCT-C treatment groups. Similarly, administration of RCT-C reduced HMGB-1 mRNA and protein expression (P <0.01). CONCLUSIONS:RCT-C exerts a neuroprotective effect by reducing cleaved caspase-3- and caspase-9a-related apoptosis. Decreased HMGB-1 mRNA and protein expression in the RCT-C groups corresponds to its anti-inflammatory effect. HMGB-1 recombinant protein administration impaired the neuroprotective and immunosuppressive effect of RCT-C. This finding lends credence that RCT-C modulates the HMGB-1-related pathway and attenuates brain apoptosis in the pathogenesis of SAH.
journal_name
World Neurosurgjournal_title
World neurosurgeryauthors
Chang CZ,Wu SC,Kwan AL,Lin CLdoi
10.1016/j.wneu.2015.08.071subject
Has Abstractpub_date
2016-02-01 00:00:00pages
349-60eissn
1878-8750issn
1878-8769pii
S1878-8750(15)01087-6journal_volume
86pub_type
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journal_title:World neurosurgery
pub_type: 杂志文章
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journal_title:World neurosurgery
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journal_title:World neurosurgery
pub_type: 杂志文章,评审
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journal_title:World neurosurgery
pub_type: 杂志文章,评审
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journal_title:World neurosurgery
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journal_title:World neurosurgery
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journal_title:World neurosurgery
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journal_title:World neurosurgery
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pub_type: 杂志文章,多中心研究
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journal_title:World neurosurgery
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journal_title:World neurosurgery
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doi:10.1016/j.wneu.2018.09.095
更新日期:2018-12-01 00:00:00
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journal_title:World neurosurgery
pub_type: 杂志文章,meta分析
doi:10.1016/j.wneu.2018.06.076
更新日期:2018-09-01 00:00:00
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journal_title:World neurosurgery
pub_type: 杂志文章
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journal_title:World neurosurgery
pub_type: 杂志文章,评审
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更新日期:2016-11-01 00:00:00
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journal_title:World neurosurgery
pub_type: 杂志文章
doi:10.1016/j.wneu.2015.01.042
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pub_type: 杂志文章
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更新日期:2019-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.wneu.2018.08.131
更新日期:2018-12-01 00:00:00
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journal_title:World neurosurgery
pub_type: 杂志文章
doi:10.1016/j.wneu.2016.04.103
更新日期:2016-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.wneu.2017.07.095
更新日期:2017-11-01 00:00:00
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journal_title:World neurosurgery
pub_type: 杂志文章
doi:10.1016/j.wneu.2017.09.014
更新日期:2017-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-05-01 00:00:00
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journal_title:World neurosurgery
pub_type: 杂志文章
doi:10.1016/j.wneu.2009.06.001
更新日期:2010-02-01 00:00:00
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journal_title:World neurosurgery
pub_type: 杂志文章,评审
doi:10.1016/j.wneu.2011.05.037
更新日期:2011-12-01 00:00:00
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journal_title:World neurosurgery
pub_type: 杂志文章
doi:10.1016/j.wneu.2017.04.070
更新日期:2017-07-01 00:00:00