Vagus nerve stimulation in various stages of stroke and associated functional impairments: A review

Stroke remains a leading cause of long-term disability and mortality, emphasizing the need for innovative rehabilitation strategies that address recovery across different stages. Vagus nerve stimulation (VNS), including both invasive and non-invasive techniques, has emerged as a promising intervention to enhance neuroprotection and functional recovery in stroke rehabilitation. This review synthesizes preclinical and clinical research on VNS, highlighting its mechanisms, applications, and challenges in stroke treatment. VNS influences key neurophysiological processes, including anti-inflammatory responses mediated by the α7 nicotinic acetylcholine receptor, modulation of apoptotic pathways, reduction of oxidative stress, and enhancement of neuroplasticity and angiogenesis. Importantly, VNS exerts significant effects on glial cells, particularly microglia and astrocytes, which are crucial for neuroinflammation modulation and neural repair. Clinical evidence supports the use of VNS in improving motor function, cognitive performance, and emotional well-being, with significant benefits noted when VNS is combined with task-specific training. Despite these promising findings, variability in patient response, optimal stimulation parameters, and long-term efficacy remain areas for further investigation. Identifying biomarkers and refining stimulation protocols are crucial to tailoring VNS treatment and maximizing therapeutic outcomes. This review underscores the potential of VNS as an adjunctive therapy in stroke cure and advocates for continued research to integrate personalized, technology-driven approaches for comprehensive patient care.