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...
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doaj-34ee7b82fca043e0acdbd937550eab212021-03-05T00:07:52ZengMDPI AGBrain Sciences2076-34252021-03-011132532510.3390/brainsci11030325Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced ThrombosisFatima M. Shakova0Yuliya I. Kirova1Denis N. Silachev2Galina A. Romanova3Sergey G. Morozov4Institute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, 125315 Moscow, RussiaInstitute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, 125315 Moscow, RussiaA.N. Belozersky Research Institute of Physico-Chemical Biology, Moscow State University, Leninskye Gory 1, Bldg. 40, 119992 Moscow, RussiaInstitute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, 125315 Moscow, RussiaInstitute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, 125315 Moscow, RussiaThe 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 Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) and Semax (ACTH<sub>(</sub><sub>4</sub><sub>–</sub><sub>7) </sub>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, angiogenesis, 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 reflected 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.https://www.mdpi.com/2076-3425/11/3/325focal ischemiaprefrontal cerebral cortexPGC-1αMexidolSemaxneuroprotection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fatima M. Shakova Yuliya I. Kirova Denis N. Silachev Galina A. Romanova Sergey G. Morozov |
spellingShingle |
Fatima M. Shakova Yuliya I. Kirova Denis N. Silachev Galina A. Romanova Sergey G. Morozov Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis Brain Sciences focal ischemia prefrontal cerebral cortex PGC-1α Mexidol Semax neuroprotection |
author_facet |
Fatima M. Shakova Yuliya I. Kirova Denis N. Silachev Galina A. Romanova Sergey G. Morozov |
author_sort |
Fatima M. Shakova |
title |
Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis |
title_short |
Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis |
title_full |
Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis |
title_fullStr |
Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis |
title_full_unstemmed |
Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis |
title_sort |
protective effects of pgc-1α activators on ischemic stroke in a rat model of photochemically induced thrombosis |
publisher |
MDPI AG |
series |
Brain Sciences |
issn |
2076-3425 |
publishDate |
2021-03-01 |
description |
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 Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) and Semax (ACTH<sub>(</sub><sub>4</sub><sub>–</sub><sub>7) </sub>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, angiogenesis, 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 reflected 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. |
topic |
focal ischemia prefrontal cerebral cortex PGC-1α Mexidol Semax neuroprotection |
url |
https://www.mdpi.com/2076-3425/11/3/325 |
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