Expansion of plasma MicroRNAs over the first month following human stroke

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Stroke triggers complex molecular events impacting neural repair and secondary degeneration.
• MicroRNA (miRNA) expression dynamics during human stroke recovery remain largely uncharacterized.
• Understanding miRNA profiles is crucial for identifying biomarkers and therapeutic targets post-stroke.

Purpose of the Study:

• To characterize miRNA expression profiles in plasma following ischemic stroke in humans.
• To investigate the temporal changes in miRNA expression from acute injury through the early repair phase (5, 15, and 30 days post-stroke).
• To identify specific brain-enriched miRNAs associated with stroke-induced apoptosis and subsequent neuroprotection.

Main Methods:

• Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze the expression of 754 miRNAs.
• Plasma samples were collected from discovery (n=55) and validation (n=48) cohorts at 5, 15, and 30 days post-ischemic stroke.
• Samples were compared to age-, sex-, race-, and comorbidity-matched healthy controls.

Main Results:

• Eight miRNAs showed consistent significant alterations across all time points in both cohorts.
• The number of significantly dysregulated miRNAs increased substantially from day 5 (19 miRNAs) to days 15 (50 miRNAs) and 30 (57 miRNAs).
• Twelve brain-enriched miRNAs were significantly altered, with many linked to apoptosis early post-stroke and others suggesting a transition to synapse regulation and neuronal protection by day 30.

Conclusions:

• Stroke induces dynamic changes in plasma miRNA expression, extending beyond the acute phase.
• Specific brain-enriched miRNAs are implicated in the post-stroke transition from cell death to neuroprotective processes.
• These identified miRNAs represent potential biomarkers for stroke progression and targets for future therapeutic interventions aimed at promoting neural repair.