Abstract:
:Transient receptor potential vanilloid 1 (TRPV1) is expressed widely in the central nervous system and is activated by various stimuli. Inhibiting TRPV1 has neuroprotective effects in cerebral ischemia. The role of inhibiting TRPV1 to maintain blood-brain barrier (BBB) integrity after traumatic brain injury (TBI) remains unclear, however. Therefore, we investigated the effects of capsazepine-mediated TRPV1 inhibition on the BBB in a mouse model of TBI. Adult male C57BL/6 mice underwent controlled cortical impact injury and received capsazepine (1 μmol/kg body weight, twice daily, intraperitoneally) until sacrifice. Further, mouse brain microvascular endothelial (bEnd.3) cells were cultured and underwent biaxial stretch injury to investigate the mechanisms underlying the protective effects of capsazepine. The TRPV1 expression was upregulated in the pericontusional area after TBI, peaking at 24 h post-TBI. Capsazepine-treated mice demonstrated decreased brain edema (p = 0.010), Evans Blue extravasation (p = 0.001), tissue hemoglobin levels (p = 0.002), and loss of tight junction proteins (p = 0.016 ZO-1 expression; p = 0.013 occludin expression) after TBI compared with the vehicle-treated group. Capsazepine significantly alleviated early-stage apoptosis by attenuating activation of JNK, P38, and caspase-3, resulting in a protective effect on the level of ZO-1 in bEnd.3 cells after stretch injury. We conclude that the expression of TRPV1 is upregulated after TBI, and inhibition of TRPV1 attenuated disruption of the BBB in a mouse model of TBI, at least partly, through its antiapoptotic effects on brain endothelial cells. Blocking TRPV1 may be a promising pharmacotherapeutic intervention to protect against BBB disruption after TBI.
journal_name
J Neurotraumajournal_title
Journal of neurotraumaauthors
Yang DX,Jing Y,Liu YL,Xu ZM,Yuan F,Wang ML,Geng Z,Tian HLdoi
10.1089/neu.2018.5942subject
Has Abstractpub_date
2019-04-15 00:00:00pages
1279-1290issue
8eissn
0897-7151issn
1557-9042journal_volume
36pub_type
杂志文章abstract::Spinal cord injury (SCI) results in marked atrophy and dysfunction of skeletal muscle. There are currently no effective treatments for SCI-induced muscle atrophy or the dysfunction of the remaining muscle tissue. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4 (Nox4) produces reactive oxygen species (ROS...
journal_title:Journal of neurotrauma
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journal_title:Journal of neurotrauma
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journal_title:Journal of neurotrauma
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更新日期:1996-09-01 00:00:00
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journal_title:Journal of neurotrauma
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journal_title:Journal of neurotrauma
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abstract::Minimal traumatic brain injury (mTBI) is partially defined by the existence of retrograde amnesia and is associated with microscopic bleeds containing activated coagulation factors. In a previous study, we have found that mTBI immediately releases thrombin-like activity in the brain, which induces amnesia by activatin...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
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更新日期:2016-10-15 00:00:00
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journal_title:Journal of neurotrauma
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更新日期:2020-01-15 00:00:00
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
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更新日期:1997-01-01 00:00:00
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journal_title:Journal of neurotrauma
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journal_title:Journal of neurotrauma
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pub_type: 杂志文章,meta分析,评审
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journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
doi:
更新日期:1992-03-01 00:00:00
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更新日期:2011-09-01 00:00:00
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2010.1493
更新日期:2011-03-01 00:00:00
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journal_title:Journal of neurotrauma
pub_type: 杂志文章,多中心研究
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更新日期:2008-06-01 00:00:00
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journal_title:Journal of neurotrauma
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journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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更新日期:1996-10-01 00:00:00
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
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journal_title:Journal of neurotrauma
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journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
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