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New PAR1 agonist peptide demonstrates protective action in a mouse model of photothrombosis-induced brain ischemiaстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 29 июля 2020 г.
- Авторы: Galkov Maksim, Kiseleva Ekaterina, Gulyaev Mikhail, Sidorova Maria, Gorbacheva Liubov
- Журнал: Frontiers in neuroscience
- Том: 14
- Год издания: 2020
- Издательство: Frontiers Research Foundation
- Местоположение издательства: Switzerland
- Первая страница: 1
- Последняя страница: 12
- DOI: 10.3389/fnins.2020.00335
- Аннотация: Protease-activated receptors (PARs) are involved not only in hemostasis but also inthe development of ischemic brain injury. In the present work, we examined in vivoeffects of a new peptide (AP9) composing Asn47-Phen55 of PAR1 “tethered ligand”generated by activated protein C. We chose a mouse model of photothrombosis (PT)-induced ischemia to assess AP9 effects in vivo. To reveal the molecular mechanism ofAP9 action, mice lacking b-arrestin-2 were used. AP9 was injected intravenously once10 min before PT at doses of 0.2, 2, or 20 mg/kg, or twice, that is, 10 min beforeand 1 h after PT at a dose of 20 mg/kg. Lesion volume was measured by magneticresonance imaging and staining of brain sections with tetrazolium salt. Neurologic deficitwas estimated using the cylinder and the grid-walk tests. Blood–brain barrier (BBB)disruption was assessed by Evans blue dye extraction. Eosin-hematoxylin staining andimmunohistochemical staining were applied to evaluate the number of undamagedneurons and activated glial cells in the penumbra. A single administration of AP9(20 mg/kg), as well as its two injections (20 mg/kg), decreased brain lesion volume.A double administration of AP9 also reduced BBB disruption and neurological deficit inmice. We did not observe the protective effect of AP9 in mice lacking b-arrestin-2 afterPT. Thus, we demonstrated for the first time protective properties of a PAR1 agonistpeptide, AP9, in vivo. b-Arrestin-2 was required for the protective action of AP9 inPT-induced brain ischemia.
- Добавил в систему: Галков Максим Дмитриевич