Abstract DP117: Vagus Nerve Stimulation in Acute Stroke: Central Anti-inflammatory but Peripheral Cytokine Elevation

Introduction: Ischemic stroke triggers local brain inflammation and systemic inflammatory "spillover" affecting prognosis. Neuronal injury releases DAMPs activating microglia/astrocytes, inducing cytokines, disrupting blood-brain barrier, and causing peripheral immune infiltration. VNS modulates sympathetic-parasympathetic balance with adjustable parameters. Clinical studies show conflicting results on peripheral inflammatory factors. This study investigates VNS central anti-inflammatory mechanisms and peripheral factor elevation. Hypothesis: VNS bidirectionally regulates immune responses: centrally inhibiting microglia responses and complement activation, maintaining endothelial stability; peripherally modulating inflammation-nerve axis, mitigating immune suppression with beneficial 24h factor elevation. Methods: C57BL/6 male mice (22-25g) were divided into control, model, and treatment groups. tMCAO was performed in latter groups. All received vagal stimulators. Groups 1-2 received sham stimulation; group 3 received bipolar stimulation (0.5ms, 20Hz, 200μs) for 30s with 4.5min intervals, 1h daily. Inflammatory factors measured at 24/48h using MSD platform. TTC staining, rotarod, cylinder test, Clark score evaluated function. Results: VNS reduces infarct volume in tMCAO mice and improves neurological function. TTC staining showed tMCAO mice had significant infarction with decreased neurofunctional scores, motor function, and balance versus controls. VNS reduced infarct volume (Fig1a) and improved these outcomes and body weight(Fig1b–d) . VNS reduces central complement activation and proinflammatory factor release, improving acute-phase neuroinflammation. VNS decreased C3/C5 expression (Fig2a) and inflammatory factors in ischemic penumbra at 24h, converging at 48h (Fig3). KEGG showed inflammatory pathway downregulation(Fig2b). VNS increases peripheral inflammatory markers, reducing negative effects of peripheral immune suppression. VNS upregulated peripheral inflammatory factors at 24h (p<0.05) but not 48h (Fig3). RNA analysis showed reduced viral infection in VNS-treated mice (Fig2b), suggesting beneficial regulation. Conclusion: In conclusion, VNS exhibits bidirectional inflammatory regulation, centrally reducing neuroinflammation while peripherally upregulating beneficial inflammatory markers, optimizing inflammation-immunity balance for ischemic stroke therapy.