Brain-Body Interactions in Ischemic Stroke: VNS Reprograms Microglia and FNS Enhances Cerebellar Neuroprotection

Stroke significantly impacts mortality and long-term disability, necessitating effective rehabilitation strategies to enhance recovery. This review examines the roles of vagus nerve stimulation (VNS) and fastigial nucleus stimulation (FNS) in facilitating ischemic stroke recovery through brain-body interactions. VNS enhances ischemic stroke recovery by reprogramming microglia from proinflammatory (M1) to neuroprotective (M2) phenotypes, reducing neuroinflammation and promoting tissue repair via neurotrophic factors. It has shown promise in clinically improving chronic upper limb deficits when combined with rehabilitation therapies. Conversely, FNS provides cerebellar-mediated neuroprotection by mainly mitigating excitotoxic damage and inflammatory responses independent of cerebral blood flow alterations, as evidenced by preclinical models of middle cerebral artery occlusion. By integrating VNS-driven immunomodulation with FNS-mediated excitotoxicity suppression, this review highlights their synergistic potential to improve rehabilitation outcomes for ischemic stroke survivors. Biomarker-guided protocols: VNS for cortical/subcortical ischemic deficits and FNS for cerebellar network recovery are advocated to address postischemic disability via anti-inflammatory rewiring, neuroplasticity enhancement, and cerebellar-thalamocortical circuit stabilization. Critical gaps remain in hemorrhagic stroke, where FNS’s excitotoxicity suppression may destabilize clots, necessitating subtype-specific safety validations.