Academic Journal
Melatonin against acute ischaemic stroke dependently via suppressing both inflammatory and oxidative stress downstream signallings
العنوان: | Melatonin against acute ischaemic stroke dependently via suppressing both inflammatory and oxidative stress downstream signallings |
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المؤلفون: | Chen, Kuan‐Hung, Lin, Kun‐Chen, Ko, Sheung‐Fat, Chiang, John Y., Guo, Jun, Yip, Hon‐Kan |
المساهمون: | Chang Gung Memorial Hospital |
المصدر: | Journal of Cellular and Molecular Medicine ; volume 24, issue 18, page 10402-10419 ; ISSN 1582-1838 1582-4934 |
بيانات النشر: | Wiley |
سنة النشر: | 2020 |
المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
الوصف: | This study tested the hypothesis that melatonin (Mel) therapy preserved the brain architectural and functional integrity against ischaemic stroke (IS) dependently through suppressing the inflammatory/oxidative stress downstream signalling pathways. Adult male B6 (n = 6 per each B6 group) and TLR4 knockout (ie TLR4 −/− ) (n = 6 per each TLR4 −/− group) mice were categorized into sham control (SC B6 ), SC TLR4−/− , IS B6 , IS TLR4−/− , IS B6 + Mel (i.p. daily administration) and IS TLR4−/− + Mel (i.p. daily administration). By day 28 after IS, the protein expressions of inflammatory (HMBG1/TLR2/TLR4/MAL/MyD88/RAM TRIF/TRAF6/IKK‐α/p‐NF‐κB/nuclear‐NF‐κB/nuclear‐IRF‐3&7/IL‐1β/IL‐6/TNF‐α/IFN‐γ) and oxidative stress (NOX‐1/NOX‐2/ASK1/p‐MKK4&7/p‐JNK/p‐c‐JUN) downstream pathways as well as mitochondrial‐damaged markers (cytosolic cytochrome C/cyclophilin D/SRP1/autophagy) were highest in group IS B6 , lowest in groups SC B6 and SC TLR4−/− , lower in group IS TLR4−/− + Mel than in groups IS TLR4−/− and IS B6 + Mel and lower in group IS B6 + Mel than in group IS TLR4−/− (all P < .0001). The brain infarct volume, brain infarct area and the number of inflammatory cells in brain (CD14/F4‐88) and in circulation (MPO+//Ly6C+/CD11b+//Ly6G+/CD11b+) exhibited an identical pattern, whereas the neurological function displayed an opposite pattern of inflammatory protein expression among the six groups (all P < .0001). In conclusion, TLR inflammatory and oxidative stress signallings played crucial roles for brain damage and impaired neurological function after IS that were significantly reversed by Mel therapy. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
DOI: | 10.1111/jcmm.15654 |
الاتاحة: | http://dx.doi.org/10.1111/jcmm.15654 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fjcmm.15654 https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.15654 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jcmm.15654 |
Rights: | http://creativecommons.org/licenses/by/4.0/ |
رقم الانضمام: | edsbas.BF61D6D9 |
قاعدة البيانات: | BASE |
DOI: | 10.1111/jcmm.15654 |
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