The role of miR-10b-5p/brain-derived neurotrophic factor axis deregulation in poststroke epileptogenesis

Poststroke epilepsy (PSE) is a common complication following stroke and is associated with increased mortality and worse functional outcomes. There is no biomarker sufficiently to predict PSE, and antiseizure medications are initiated after the first unprovoked seizure. Early identification of patients at high risk for PSE is needed to consider preventive measures and improve management strategies.

Illumina miRNA sequencing was performed on serum collected at follow-ups of patients with PSE and compared to ischemic stroke patients without epilepsy and patients with epilepsy without stroke (N = 24). Differentially expressed miRNAs were validated in a larger cohort (N = 53) by qPCR, and target prediction was performed in silico. Brain-derived neurotrophic factor (BDNF) levels were measured using ELISA and correlated with clinical parameters.

miRNA profiling revealed significant differences among the groups, with miR-10b-5p expression reduced in PSE patients compared to those with stroke alone. miR-486-5p was significantly reduced in PSE patients compared to epilepsy patients. qPCR validation confirmed miR-10b-5p as a potential biomarker candidate to distinguish PSE patients from stroke patients without PSE. BDNF, a key regulator of post-stroke recovery and epileptogenesis, was identified as a primary target of miR-10b-5p. While no group-level differences in serum BDNF concentrations were observed, BDNF levels correlated with disease duration and seizure latency exclusively in the PSE group.

Importantly, as samples were obtained during follow-up rather than the acute post-stroke phase, our results indicate an involvement of the miR-10b-5p/BDNF axis in long-term post-stroke remodeling or general PSE susceptibility rather than a predictive biomarker. However, the miR-10b-5p/BDNF axis may represent a biologically plausible pathway associated with post-stroke epileptogenesis and impaired post-ischemic recovery. Prospective longitudinal studies with early post-stroke sampling are required to determine its predictive value.