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Published on: June 22, 2022
Neuroprotective Therapeutic Potential of microRNA-149-5p against Murine Ischemic Stroke
Samira Vahidi1, Mohammad-Reza Bigdeli2,3, Hosein Shahsavarani4
1Department of Animal Science and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Abstract:
Ischemic stroke resulting from blockade of brain vessels lacks effective treatments, prompting exploration for potential therapies. Among promising candidates, microRNA-149 (miR-149) has been investigated for its role in alleviating oxidative stress, inflammation, and neurodegeneration associated with ischemic conditions. To evaluate its therapeutic effect, male Wistar rats were categorized into five groups, each consisting of 27 rats: sham, MCAO, lentiviral control, lentiviral miR-149, and miR149-5p mimic. Treatments were microinjected intracerebroventricularly (ICV) (right side), and ischemia was induced using middle cerebral artery occlusion (MCAO) procedure. Post-MCAO, neurological function, histopathological changes, blood-brain barrier (BBB) permeability, cerebral edema, and mRNA levels of Fas ligand (Faslg) and glutamate ionotropic NMDA receptor 1 (GRIN1) were assessed, alongside biochemical assays. MiR-149 administration improved neurological function, reduced brain damage, preserved BBB integrity, and attenuated cerebral edema. Upregulation of miR149-5p decreased Faslg and GRIN1 expression in ischemic brain regions. MiR-149 also reduced oxidative stress, enhanced antioxidant activity, decreased caspase-1 and - 3 activity, and modulated inflammatory factors in ischemic brain regions. Moreover, DNA fragmentation as an index of cell death decreased following miR-149 treatment. In conclusion, the study underscores miR-149 potential as a neuroprotective agent against ischemic stroke, showcasing its efficacy in modulating various mechanisms and supporting its candidacy as a promising therapeutic target for innovative strategies in stroke treatment.
Insights
MicroRNA-149 (miR-149) shows promise as a neuroprotective therapy for ischemic stroke. This study found miR-149 treatment improved neurological function and reduced brain damage in rats, highlighting its therapeutic potential.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Ischemic stroke lacks effective treatments, necessitating novel therapeutic strategies.
- MicroRNA-149 (miR-149) is being explored for its potential to mitigate oxidative stress, inflammation, and neurodegeneration in ischemic conditions.
Purpose of the Study:
- To evaluate the therapeutic efficacy of miR-149 in a rat model of ischemic stroke.
- To investigate the effects of miR-149 on neurological function, brain damage, and key molecular pathways.
Main Methods:
- Male Wistar rats underwent middle cerebral artery occlusion (MCAO) to induce ischemia.
- Treatments, including lentiviral miR-149 and miR149-5p mimic, were administered intracerebroventricularly.
- Neurological function, histopathology, blood-brain barrier permeability, cerebral edema, and gene/protein expression were assessed.
Main Results:
- miR-149 administration significantly improved neurological function and reduced brain damage and cerebral edema.
- It preserved blood-brain barrier integrity and decreased the expression of Fas ligand (Faslg) and GRIN1.
- miR-149 treatment reduced oxidative stress, enhanced antioxidant activity, decreased caspase activity, and modulated inflammatory factors.
Conclusions:
- miR-149 demonstrates significant neuroprotective effects against ischemic stroke in rats.
- It acts by modulating oxidative stress, inflammation, apoptosis, and specific molecular targets.
- miR-149 represents a promising therapeutic candidate for innovative stroke treatment strategies.
