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Author Spotlight: Establishing a Reliable Distal MCA Occlusion Model in Mice for Stroke Research
Published on: December 15, 2023
MicroRNA miR-21 Decreases Post-stroke Brain Damage in Rodents
Mary S Lopez1,2, Kahlilia C Morris-Blanco1, Nancy Ly1
1Department of Neurological Surgery, University of Wisconsin, Madison, WI, 53792, USA.
Abstract:
Due to their role in controlling translation, microRNAs emerged as novel therapeutic targets to modulate post-stroke outcomes. We previously reported that miR-21 is the most abundantly induced microRNA in the brain of rodents subjected to preconditioning-induced cerebral ischemic tolerance. We currently show that intracerebral administration of miR-21 mimic decreased the infarct volume and promoted better motor function recovery in adult male and female C57BL/6 mice subjected to transient middle cerebral artery occlusion. The miR-21 mimic treatment is also efficacious in aged mice of both sexes subjected to focal ischemia. Mechanistically, miR-21 mimic treatment decreased the post-ischemic levels of several pro-apoptotic and pro-inflammatory RNAs, which might be responsible for the observed neuroprotection. We further observed post-ischemic neuroprotection in adult mice administered with miR-21 mimic intravenously. Overall, the results of this study implicate miR-21 as a promising candidate for therapeutic translation after stroke.
Insights
MicroRNA-21 (miR-21) administration reduced stroke damage and improved motor function in mice. This microRNA shows promise as a novel therapeutic target for stroke recovery.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs regulate gene expression and are potential therapeutic targets for stroke.
- miR-21 is highly induced in the brain following cerebral ischemic tolerance.
Purpose of the Study:
- To investigate the neuroprotective effects of miR-21 mimic treatment in a mouse model of stroke.
- To explore the therapeutic potential of miR-21 for modulating post-stroke outcomes.
Main Methods:
- Intracerebral and intravenous administration of miR-21 mimic in adult and aged male and female C57BL/6 mice subjected to transient middle cerebral artery occlusion.
- Assessment of infarct volume and motor function recovery.
- Analysis of post-ischemic RNA levels.
Main Results:
- Intracerebral miR-21 mimic administration significantly decreased infarct volume and improved motor function in mice.
- Treatment was effective in both young and aged mice, and via both intracerebral and intravenous routes.
- miR-21 mimic treatment reduced pro-apoptotic and pro-inflammatory RNA levels post-stroke.
Conclusions:
- miR-21 demonstrates significant neuroprotective effects in preclinical stroke models.
- miR-21 holds promise as a therapeutic agent for stroke treatment.
- Further research into miR-21-based therapies for stroke is warranted.
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