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Introduction: Ischemic stroke induces neuroinflammation and neuronal injury, potentially contributing to cognitive impairment. However, the relationship between circulating inflammatory and neuronal injury biomarkers and early cognitive outcomes after mild to moderate stroke remains unclear. This study investigated plasma biomarkers associated with stroke severity and cognition. Methods: Forty-three individuals with mild to moderate ischemic stroke and age-, sex-, and education-matched controls were evaluated within seven days. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS). Cognition was assessed using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Visual/Verbal Memory Test (VMT). Neuronal injury and inflammatory markers were measured by ELISA. Group comparisons, linear regression, and ROC analyses were performed. Results: Post-stroke participants showed impairments in executive functions, immediate memory, learning, and recognition versus controls. Ubiquitin C-terminal hydrolase L1 (UCHL1), neuron-specific enolase (NSE), and lipocalin levels were increased, whereas S100 calcium-binding protein B (S100B), CCL3, CCL4, CCL5, and CXCL8 were decreased. Higher NSE and lipocalin levels were associated with poorer FAB and VMT performance. Conversely, CXCL8 correlated positively with FAB, immediate memory, and learning. MIF and myeloperoxidase (MPO) discriminated participants with executive dysfunction and impaired immediate recall, respectively (AUC=0.815 and 0.830). Increased S100B and NSE and decreased CCL3 and CCL5 were associated with greater stroke severity. Conclusion: Plasma NSE, CXCL8, MIF, MPO, and lipocalin may represent potential predictive and prognostic biomarkers of cognitive impairment after mild to moderate ischemic stroke. These exploratory findings require validation in longitudinal studies and larger cohorts.
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