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New PAR1 Agonist Peptide Demonstrates Protective Action in a Mouse Model of Photothrombosis-Induced Brain Ischemia

Galkov M., Kiseleva E., Gulyaev M., Sidorova M., Gorbacheva L.
Тип документаJournal Article
Дата публикации2020-05-19
Название журналаFrontiers in Neuroscience
ИздательFrontiers Media S.A.
Квартиль по SCImagoQ2
Квартиль по Web of ScienceQ2
Импакт-фактор 20215.15
ISSN16624548, 1662453X
General Neuroscience
Краткое описание
Protease-activated receptors (PARs) are involved not only in hemostasis but also in the development of ischemic brain injury. In the present work, we examined in vivo effects 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 of AP9 action, mice lacking β-arrestin-2 were used. AP9 was injected intravenously once 10 min before PT at doses of 0.2, 2, or 20 mg/kg, or twice, that is, 10 min before and 1 h after PT at a dose of 20 mg/kg. Lesion volume was measured by magnetic resonance imaging and staining of brain sections with tetrazolium salt. Neurologic deficit was estimated using the cylinder and the grid-walk tests. Blood–brain barrier (BBB) disruption was assessed by Evans blue dye extraction. Eosin-hematoxylin staining and immunohistochemical staining were applied to evaluate the number of undamaged neurons 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 in mice. We did not observe the protective effect of AP9 in mice lacking β-arrestin-2 after PT. Thus, we demonstrated for the first time protective properties of a PAR1 agonist peptide, AP9, in vivo. β-Arrestin-2 was required for the protective action of AP9 in PT-induced brain ischemia.
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1. Galkov M. и др. New PAR1 Agonist Peptide Demonstrates Protective Action in a Mouse Model of Photothrombosis-Induced Brain Ischemia // Frontiers in Neuroscience. 2020. Т. 14.
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TY - JOUR

DO - 10.3389/fnins.2020.00335

UR - http://dx.doi.org/10.3389/fnins.2020.00335

TI - New PAR1 Agonist Peptide Demonstrates Protective Action in a Mouse Model of Photothrombosis-Induced Brain Ischemia

T2 - Frontiers in Neuroscience

AU - Galkov, Maksim

AU - Kiseleva, Ekaterina

AU - Gulyaev, Mikhail

AU - Sidorova, Maria

AU - Gorbacheva, Liubov

PY - 2020

DA - 2020/05/19

PB - Frontiers Media SA

VL - 14

SN - 1662-453X

ER -

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@article{2020,

doi = {10.3389/fnins.2020.00335},

url = {https://doi.org/10.3389%2Ffnins.2020.00335},

year = 2020,

month = {may},

publisher = {Frontiers Media {SA}},

volume = {14},

author = {Maksim Galkov and Ekaterina Kiseleva and Mikhail Gulyaev and Maria Sidorova and Liubov Gorbacheva},

title = {New {PAR}1 Agonist Peptide Demonstrates Protective Action in a Mouse Model of Photothrombosis-Induced Brain Ischemia}

}

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Galkov, Maksim et al. “New PAR1 Agonist Peptide Demonstrates Protective Action in a Mouse Model of Photothrombosis-Induced Brain Ischemia.” Frontiers in Neuroscience 14 (2020): n. pag. Crossref. Web.