A different view on the platelet aggregation inhibitor clopidogrel - a well-suitable anti-oedema agent in a preclinical model of brain injury?

Basit Öğe Kaydı
dc.authorid0000-0001-7702-2441
dc.authorid0000-0002-9704-6173
dc.authorid0000-0002-5072-132X
dc.authorid0000-0002-1079-8832
dc.authorid0000-0002-7059-1884
dc.authorid0000-0001-6494-8923
dc.contributor.authorGünal, Mehmet Yalçın
dc.contributor.authorYuluğ, Burak
dc.contributor.authorÇağlayan, Berrak
dc.contributor.authorOzansoy, Mehmet
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorKeskin, İlknur
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned2019-12-31T11:18:14Z
dc.date.available2019-12-31T11:18:14Z
dc.date.issued2019
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Histoloji ve Embriyoloji Ana Bilim Dalı
dc.description.abstractAim: The neuroprotective effects of clopidogrel have already been shown in various experimental models. Taking into account the fact that clopidogrel is well tolerated and approved for use in various clinical settings, it can be an attractive candidate for further clinical investigations, especially when the anti-oedema effect appears to be a reasonable adjuvant strategy, such as in brain injury (BI). Here we aimed to examine the neuroprotective role of clopidogrel in BI. Methods: To investigate the effects of clopidogrel, we induced BI in mice using a cold trauma model and evaluated the underlying cell survival/death mechanisms via cresyl violet, TUNEL staining and western blot analysis. Results: Clopidogrel at a dose of 3 mg/kg led to a significant reduction in brain swelling. Similar decreases were observed with 10 mg/kg and 30 mg/kg of clopidogrel. We also have shown that clopidogrel blocks the prominent inflammatory injury pathways and exerts a significant anti-apoptotic effect (3 and 30 mg/kg), which has boon associated with increased neuronal cell survival pathways. Clopidogrel (3, 10 and 30 mg/kg) dose-dependently altered the JNK, p-38, AKT, ERK and p53 levels. Conclusion: Our findings demonstrate that clopidogrel can be a novel candidate for the reduction of post-traumatic BI and oedema. We propose that it can be applied mainly in the acute phases of cerebral ischaemia, which is characterized by haemorrhagic transformation and brain oedema.
dc.description.abstractCíl: Neuroprotektivní ú?inky klopidogrelu ji? byly prokázány na r?zn?ch experimentálních modelech. Vzhledem k tomu, ?e klopidogrel je dob?e tolerován a schválen k pou?ívání v r?zn?ch klinick?ch podmínkách, m??e b?t atraktivním kandidátem pro další klinická zkoumání, zejména v situaci, kdy se antiedematick? ú?inek jeví jako vhodná adjuvantní strategie, nap?íklad p?i poran?ní mozku. Naším zám?rem bylo prozkoumat neuroprotektivní roli klopidogrelu p?i poran?ní mozku. Metody: Pro zkoumání ú?ink? klopidogrelu jsme navodili poran?ní mozku s pou?itím modelu chladového traumatu u myší a zkoumali jsme základní mechanizmus p?e?ití/odumírání bun?k s pou?itím kresolové violeti, barvení TUNEL a anal?zy western blot. V?sledky: Klopidogrel v dávce 3 mg/kg vedl k signifi kantnímu sní?ení otoku mozku. Podobn? pokles byl pozorován p?i dávce klopidogrelu 10 mg/kg a 30 mg/kg. Rovn?? jsme prokázali, ?e klopidogrel blokoval prominentní cesty poškození zán?tem a vykazoval siln? antiaptotick? ú?inek (3 a 30 mg/kg), kter? byl spojen se zv?šenou mo?ností p?e?ití neuronov?ch bun?k. Klopidogrel (3, 10 a 30 mg/kg) m?nil dávkov? dependentním zp?sobem hladiny JNK, p-38, AKT, ERK a p53. Záv?r: Naše nálezy prokazují, ?e klopidogrel m??e b?t nov?m kandidátem pro zmírn?ní posttraumatického poran?ní mozku a edému. Domníváme se, ?e m??e b?t aplikován hlavn? v akutních fázích cerebrální ischemie, která je charakterizována hemoragickou transformací a edémem mozku.
dc.identifier.citationGünal, M. Y., Yuluğ, B., Çağlayan, B., Çetin Ozansoy, M. B., Kılıç, Ü., Keskin, İ. ... Kılıç, E. (2019). A different view on the platelet aggregation inhibitor clopidogrel - a well-suitable anti-oedema agent in a preclinical model of brain injury? Ceska A Slovenska Neurologie A Neurochirurgiei, 82(5), 526-532. https://doi.org/10.14735/amcsnn2019526
dc.identifier.doi10.14735/amcsnn2019526
dc.identifier.endpage532
dc.identifier.issn1210-7859
dc.identifier.issn1802-4041
dc.identifier.issue5
dc.identifier.scopusqualityQ3
dc.identifier.startpage526
dc.identifier.urihttps://doi.org/10.14735/amcsnn2019526
dc.identifier.urihttps://hdl.handle.net/20.500.12511/4837
dc.identifier.volume82
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherCzech Medical Soc
dc.relation.ispartofCeska A Slovenska Neurologie A Neurochirurgieen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectClopidogrel
dc.subjectBrain Injury
dc.subjectNeuroprotective Effect
dc.subjectBrain Swelling
dc.subjectInfarct Volume
dc.subjectCell Survival Pathways
dc.subjectKlopidogrel
dc.subjectPoran?ní Mozku
dc.subjectNeuroprotektivní Ú?inek
dc.subjectOtok Mozku
dc.subjectObjem İnfarktu
dc.subjectMechanizmy P?e?ití Bun?k
dc.titleA different view on the platelet aggregation inhibitor clopidogrel - a well-suitable anti-oedema agent in a preclinical model of brain injury?
dc.title.alternativeJin? pohled na inhibitor agregace krevních desti?ek klopidogrel – vhodné antiedematikum v p?edklinickém modelu poran?ní mozku?
dc.typeArticle

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
Gunal, Mehmet Yalcın-2019.pdf
Boyut:
208.62 KB
Biçim:
Adobe Portable Document Format
Açıklama:
Tam Metin / Full Text
İndir
Lisans paketi
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
license.txt
Boyut:
1.44 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

Makale Koleksiyonu
Makale Koleksiyonu
Makale Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu