Reduced Expression of Selected Exosomal MicroRNAs Is Associated with Poor Outcomes in Patients with Acute Stroke Receiving Reperfusion Therapy—Preliminary Study

TL;DR

This study finds that lower levels of certain microRNAs in stroke patients receiving combined reperfusion therapy are linked to worse recovery outcomes.

Contribution

The study identifies specific exosomal miRNAs associated with poor outcomes in acute stroke patients undergoing reperfusion therapy.

Findings

Patients with unfavorable outcomes had reduced levels of miR-17, miR-20, miR-186, and miR-222 after combined stroke therapy.

Target genes of these miRNAs are linked to cell death, inflammation, and neurodegeneration.

Combined reperfusion therapy (rt-PA/MT) uniquely lowered DEmiRNA levels compared to other treatments.

Abstract

Reperfusion therapy uses thrombolysis and clot removal to restore blood flow in the brain after stroke; however, three months after reperfusion therapy, roughly 46% of stroke patients become independent again. MiRNAs (micro RNA) regulate cerebral ischemia/reperfusion injury, and their transfer between cells via exosomes may differentially affect recipient cells. We examined serum exosomal miRNA levels, stroke treatments, and functional outcomes in stroke patients, and we explored the potential role of estimated differentially expressed miRNA (DEmiRNA) target genes in the brain’s reaction to reperfusion after ischemia. The patients in the study received aspirin or reperfusion therapy with either intravenous thrombolysis (rt-PA), mechanical thrombectomy (MT), or a combination of both (rt-PA/MT). Serum samples were collected from stroke patients on days 1 and 10 post-stroke. Serum exosomes’ miRNA was analyzed using qRT-PCR. We identified DEmiRNAs, estimated their targets, and performed enrichment analysis. Functional outcomes were assessed using the modified Rankin Scale (mRS) on days 10 and 90 post-stroke. Among studied treatments, only rt-PA/MT lowered DEmiRNA by day 10 vs. other groups. Specifically, patients with unfavorable mRS score exhibited decreased levels of miR-17, miR-20, miR-186 and miR-222 after combined stroke therapy. Functional analysis identified target genes and pathways associated with cytoskeleton remodeling, cell death, autophagy, inflammation, and dementia. In conclusion, unfavorable stroke outcomes following poor rt-PA/MT response could result from lower miRNA expression levels, thus activating cell death and neurodegenerative processes in brain.

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