Glatiramer Acetate Effect on the Expression of MiR-21 and Let7i Via Down-Regulation of MAPK and JAK Signaling Pathways in Stroke Mice Model and PBMCs of Stroke Patients

Background: Ischemic stroke is a prominent neurodegenerative disease, characterized by a decrease in the body’s functional abilities. It is proposed that many immunity members and cells might play a role in the pathogenesis of stroke, among which microRNAs have recently attracted much attention. MicroRNAs are noncoding RNAs involved in various immune functions and disorders. The present study aimed to evaluate the effect of Glatiramer acetate on microRNAs in stroke through immune signaling pathways. Methods: In this study, photothrombotic (PT) stroke was induced in adult C57BL/6J mice. After three days of recovery, the mice were treated with Glatiramer acetate on day three post-stroke. Simultaneously, the peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples of the stroke patients. The expression of miR-21 and Let7i was evaluated using real-time polymerase chain reaction (PCR). Additionally, the expression of MAPK and JAK pathways was assessed by Western blot. The P value of 0.001 was considered statistically significant. Results: Glatiramer acetate decreases the expression of let-7i and miR-21 in both the stroke mice model and PBMCs of stroke patients, compared to controls. Furthermore, Western blot analysis showed that Glatiramer acetate inhibits the immune signaling pathways involving MAPK and JAK in the stroke mice model. Conclusion: In addition to its known neuroprotective effects during the acute phase of experimental stroke, Glatiramer acetate administration decreases the expression of miR-21 and let-7i via down-regulation of immune signaling pathways.