Vagus Nerve Stimulation in the Management of Neurodegenerative Diseases: A Systematic Review of Advances in Animal Research and Clinical Applications

INTRODUCTION: Vagus Nerve Stimulation (VNS) has been approved by the FDA as a treatment for epilepsy, depression, post-ischemic stroke rehabilitation, and migraine in patients. It is emerging as a potential treatment for neurodegenerative diseases. Herein, we summarize the research on VNS and its application in common neurodegenerative diseases. METHODS: A literature search was completed in PubMed, ScienceDirect, and Google Scholar using the terms: "neurodegeneration," "neuromodulation," "Vagus Nerve Stimulation," "Parkinson's Disease (PD)," "Alzheimer's Disease (AD)," "dementia," "neuroinflammation," and "cognitive dysfunction." Animal and clinical studies using VNS as a primary intervention in neurodegenerative diseases were included. RESULTS: The studies of VNS application in Parkinson's and Alzheimer's models were reviewed. In animal studies, VNS was associated with increased locomotion and balance, as well as reduced cognitive impairments. The underlying neuroprotective mechanisms included: increased dopaminergic neurons, reduced α-synuclein concentration in the brain, preservation of the nigrostriatal dopaminergic pathway, increased α7nAChR expression, reduced apoptotic markers, reduced neuroinflammation, and significant reductions in microglial and astrocytic densities. In clinical studies with small patient populations of PD or AD/mild cognitive impairment, VNS was associated with improved gait parameters and enhanced performance in memory-based tasks. DISCUSSION: Vagus Nerve Stimulation (VNS) shows neuroprotective and anti-inflammatory effects in animal models of Alzheimer's and Parkinson's disease, but clinical results remain inconsistent due to variability in treatment duration, outcome measures, and reliance on subjective assessments. Emerging physiologic biomarkers such as VSEP, EEG, and magnetoencephalography may provide more objective measures of therapeutic response. CONCLUSIONS: The systematic review highlights the potential of VNS as a therapeutic approach for managing neurodegenerative diseases. The efficacy of VNS in animal models of Parkinson's and Alzheimer's diseases involves both neuroprotection and anti-neuroinflammation, while additional protective mechanisms require further exploration.