کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6270888 | 1614743 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator RS9 attenuates brain injury after ischemia reperfusion in mice
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کلمات کلیدی
NF-κBHO-1CCAMCAOAREsHeme oxygenase-1NQO-1IRI - IRIschemia–reperfusion injury - آسیب مجدد ایسکمی-رپرفیوژنmiddle cerebral artery occlusion - انسداد شریان (سرخرگ) مغزی میانیBARD - باردBardoxolone methyl - باردکسولون متیلanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of variancecommon carotid artery - شریان کاروتید مشترکNuclear factor-kappa B - فاکتور هسته ای-کاپا BKeap-1 - فروش-1Kelch-like ECH-associated protein 1 - پروتئین مرتبط با ECH کلچ 1
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Recanalization of occluded vessels leads to ischemia-reperfusion injury (IRI), with oxidative stress as one of the main causes of injury, despite the fact that recanalization therapy is the most effective treatment for ischemic stroke. The nuclear factor erythroid 2-related factor 2 (Nrf2) is one of the transcription factors which has an essential role in protection against oxidative stress. RS9 is a novel Nrf2 activator obtained from bardoxolone methyl (BARD), an Nrf2 activator that has already been tested in a clinical trial, using a biotransformation technique. RS9 has been reported to lead to higher Nrf2 activation and less cytotoxicity than BARD. In this study, we investigated the effects of RS9 on IRI. Mice were intraperitoneally treated immediately after 2 h of transient middle cerebral artery occlusion (MCAO) with a vehicle solution or 0.2 mg/kg of RS9. Post-onset treatment of RS9 attenuated the infarct volume and improved neurological deficits 22 h after reperfusion. RS9 activated Nrf2 2 and 6 h after reperfusion and activated heme oxygenase-1 at 6 and 22 h after reperfusion. RS9 also attenuated the phosphorylation of NF-κB p65 2 and 6 h after reperfusion. Finally, RS9 improved the survival rate and neurological deficits 7 days after MCAO. Our results suggest that the activation of Nrf2 by RS9 has a neuroprotective effect, mediated by attenuating both oxidative stress and neuroinflammation, and that RS9 is an effective therapeutic candidate for the treatment of IRI.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 333, 1 October 2016, Pages 302-310
Journal: Neuroscience - Volume 333, 1 October 2016, Pages 302-310
نویسندگان
Keita Yamauchi, Yusuke Nakano, Takahiko Imai, Toshinori Takagi, Kazuhiro Tsuruma, Masamitsu Shimazawa, Toru Iwama, Hideaki Hara,