Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis
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Updated: Nov 10, 2025
Photothrombotic Ischemia: A Minimally Invasive and Reproducible Photochemical Cortical Lesion Model for Mouse Stroke Studies
Published on: June 9, 2013
Fatima M Shakova1, Yuliya I Kirova1, Denis N Silachev2,3
1Institute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, 125315 Moscow, Russia.
Abstract:
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(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, 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.
Insights
Mexidol and Semax protect against ischemic brain injury by preserving neurons and enhancing PGC-1α activity. These drugs promote neuroprotection by modulating peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) expression and nuclear translocation.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is crucial for ischemic brain tolerance and neuroprotection.
- Pharmacological agents that modulate cerebral PGC-1α are limited, presenting a therapeutic gap.
Purpose of the Study:
- To investigate the PGC-1α-modulating effects of Mexidol and Semax in a rat model of ischemic stroke.
- To assess the impact of these agents on neuronal survival and PGC-1α-dependent pathways.
Main Methods:
- A rat model of photochemical-induced thrombosis (PT) in the prefrontal cortex was established.
- Mexidol and Semax were administered, and PGC-1α expression, nuclear translocation, and downstream markers were analyzed via immunoblotting and immunohistochemistry at various time points post-PT.
Main Results:
- Photochemical-induced thrombosis (PT) suppressed PGC-1α expression and reduced neuronal count in the brain's penumbra.
- Mexidol and Semax administration preserved neuronal numbers and PGC-1α expression within neurons.
- Both drugs stimulated PGC-1α nuclear translocation and increased markers of mitochondriogenesis, angiogenesis, and synaptogenesis.
Conclusions:
- Mexidol and Semax demonstrate neuroprotective potential by modulating PGC-1α pathways in ischemic stroke.
- These findings suggest novel therapeutic strategies for ischemic brain injury through pharmacological PGC-1α activation.
