Jiný pohled na inhibitor agregace krevních destiček klopidogrel – vhodné antiedematikum v předklinickém modelu poranění mozku?

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Autoři: M. Yalcin Gunal ^1,2; B. Yulug ^2,3; B. Caglayan ^2,4; M. Ozansoy ^2,4; U. Kilic ⁵; I. Keskin ^2,6; E. Kilic ^2,4
Působiště autorů: Department of Physiology, School of, Medicine, Alanya Alaaddin Keykubat, University, Antalya, Turkey ¹; Regenerative and Restorative Medical, Research Center (REMER), University, of Istanbul-Medipol, Istanbul, Turkey ²; Department of Neurology, School of, Medicine, Alanya Alaaddin Keykubat, University, Antalya, Turkey ³; Department of Physiology, School of, Medicine, University of Istanbul-Medipol, Istanbul, Turkey ⁴; Department of Medical Biology, School of Medicine, University of, Health Sciences, Istanbul, Turkey ⁵; Department of Histology, School of, Medicine, University of Istanbul-Medipol, Istanbul, Turkey ⁶
Vyšlo v časopise: Cesk Slov Neurol N 2019; 82(5): 526-532
Kategorie: Původní práce

Souhrn

Cíl: Neuroprotektivní účinky klopidogrelu již byly prokázány na různých experimentálních modelech. Vzhledem k tomu, že klopidogrel je dobře tolerován a schválen k používání v různých klinických podmínkách, může být atraktivním kandidátem pro další klinická zkoumání, zejména v situaci, kdy se antiedematický účinek jeví jako vhodná adjuvantní strategie, například při poranění mozku. Naším záměrem bylo prozkoumat neuroprotektivní roli klopidogrelu při poranění mozku.

Metody: Pro zkoumání účinků klopidogrelu jsme navodili poranění mozku s použitím modelu chladového traumatu u myší a zkoumali jsme základní mechanizmus přežití/ odumírání buněk s použitím kresolové violeti, barvení TUNEL a analýzy western blot.

Výsledky: Klopidogrel v dávce 3 mg/ kg vedl k signifikantnímu snížení otoku mozku. Podobný pokles byl pozorován při dávce klopidogrelu 10 mg/ kg a 30 mg/ kg. Rovněž jsme prokázali, že klopidogrel blokoval prominentní cesty poškození zánětem a vykazoval silný antiaptotický účinek (3 a 30 mg/ kg), který byl spojen se zvýšenou možností přežití neuronových buněk. Klopidogrel (3, 10 a 30 mg/ kg) měnil dávkově dependentním způsobem hladiny JNK, p-38, AKT, ERK a p53.

Závěr: Naše nálezy prokazují, že klopidogrel může být novým kandidátem pro zmírnění posttraumatického poranění mozku a edému. Domníváme se, že může být aplikován hlavně v akutních fázích cerebrální ischemie, která je charakterizována hemoragickou transformací a edémem mozku.

Klíčová slova:

klopidogrel – poranění mozku – neuroprotektivní účinek – otok mozku – objem infarktu – mechanizmy přežití buněk

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