Protective effects of pgc‐1α activators on ischemic stroke in a rat model of photochemically induced thrombosis

The pharmacological induction and activation of peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (PGC‐1α), a key regulator of ischemic brain tolerance, is a promising direction in neuroprotective therapy. Pharmacological agents with known abilities to modulate cerebral PGC‐1α are scarce. This study focused on the potential PGC‐1α‐modulating activity of Mexi-dol (2‐ethyl‐6‐methyl‐3‐hydroxypyridine succinate) and Semax (ACTH(4–7) analog) in a rat model of photochemical‐induced thrombosis (PT) in the prefrontal cortex. Mexidol (100 mg/kg) was administered intraperitoneally, and Semax (25 μg/kg) was administered intranasally, for 7 days each. The expression of PGC‐1α and PGC‐1α‐dependent protein markers of mitochondriogenesis, angiogen-esis, and synaptogenesis was measured in the penumbra via immunoblotting at Days 1, 3, 7, and 21 after PT. The nuclear content of PGC‐1α was measured immunohistochemically. The suppression of PGC‐1α expression was observed in the penumbra from 24 h to 21 days following PT and re-flected decreases in both the number of neurons and PGC‐1α expression in individual neurons. Administration of Mexidol or Semax was associated with preservation of the neuron number and neuronal expression of PGC‐1α, stimulation of the nuclear translocation of PGC‐1α, and increased contents of protein markers for PGC‐1α activation. This study opens new prospects for the pharmacological modulation of PGC‐1α in the ischemic brain. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Авторы
Shakova F.M.1 , Kirova Y.I.1 , Silachev D.N. 2, 3 , Romanova G.A.1 , Morozov S.G.1
Журнал
Издательство
MDPI AG
Номер выпуска
3
Язык
Английский
Страницы
1-30
Статус
Опубликовано
Номер
325
Том
11
Год
2021
Организации
  • 1 Institute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, Moscow, 125315, Russian Federation
  • 2 A.N. Belozersky Research Institute of Physico‐Chemical Biology, Moscow State University, Leninskye Gory 1, Bldg. 40, Moscow, 119992, Russian Federation
  • 3 Histology, Embryology and Cytology Department, Peoples’ Friendship University of Russia, Miklukho‐Maklaya Str. 6, Moscow, 117198, Russian Federation
Ключевые слова
Focal ischemia; Mexidol; Neuroprotection; PGC‐1α; Prefrontal cerebral cortex; Semax
Дата создания
20.04.2021
Дата изменения
20.04.2021
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/72084/
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Другие записи

Orazmuradov A.A., Akhmatova A.N., Haddad K., Lopatin A.M., Bekbaeva I.V., Arakelyan G.A., Abitova M.Z., Kyrtikov S.I., Zokirova N.M., Lukaev A.A.
INTERNATIONAL JOURNAL OF BIOMEDICINE. INT MEDICAL RESEARCH & DEVELOPMENT CORP. Том 11. 2021. С. 65-67