Abstract DP393: Integrated Neuro-Cardiac Protection by Edaravone-Dexborneol in Vascular Dementia with Metabolic Syndrome

Background: Brain–heart interactions are increasingly recognized as critical contributors to the onset and progression of vascular dementia (VaD). Multiple microinfarctions (MMI) and chronic cerebral hypoperfusion (CCH) are major pathological drivers of VaD, often exacerbated by metabolic syndrome (MetS), which also predisposes to cardiac dysfunction. While edaravone-dexborneol (EDB) is a clinically approved neuroprotective agent with antioxidant and anti-inflammatory properties, its therapeutic potential in modulating both cognitive decline and secondary cardiac injury in VaD with MetS has not been explored. Methods: Late-adult male C57BL/6J mice underwent either MMI or BCAS combined with high-fat diet (HFD) to model VaD with or without MetS. EDB (5 or 10 mg/kg, i.p., twice daily) was administered for 14-28 days starting 24 h post-surgery. Cognitive performance was evaluated using a battery of behavioral tests; cardiac function and vascular parameters were assessed by echocardiography and Doppler ultrasound. Histopathological and molecular analyses of brain and heart were performed to assess neuronal injury, white matter integrity, fibrosis and inflammation. Correlation analyses were conducted between cognitive, cardiac, and metabolic indices. Results: Both MMI and BCAS+HFD induced multidomain cognitive deficits, microglial activation, hippocampal and white matter injury, and marked cardiac dysfunction (↓LVEF, ↓LVFS) in the absence of primary heart disease. BCAS+HFD additionally caused cardiac hypertrophy, fibrosis, inflammatory cell infiltration (↑CD32, TNF-α, MCP-1, IL-6). High-dose EDB significantly improved cognitive performance and cardiac systolic function in both models, with effects correlating positively between brain and heart outcomes. In BCAS+HFD mice, EDB reduced cardiac fibrosis and inflammatory infiltration, ameliorated hippocampal injury, and improved white matter integrity. Conclusion: We demonstrate for the first time that EDB not only mitigates cognitive impairment but also alleviates secondary cardiac dysfunction in experimental VaD, particularly in the presence of MetS. The parallel improvement of brain and heart function, coupled with reduced neuroinflammation, cardiac fibrosis, and systemic metabolic burden, underscores the central role of brain–heart crosstalk in VaD pathophysiology. These findings identify EDB as a promising dual-target therapeutic strategy for patients with VaD and cardiometabolic comorbidities.