Unveiling the Glial Cell Mechanisms Underlying Vagus Nerve StimulationInduced Neuroprotection After Ischemic Stroke

Ischemic stroke, one of the most common causes of disability due to cerebrovascular disease, is characterized by severe immune-inflammatory reactions and massive cell death resulting from ischemia-induced injury. Glial cells, such as microglia, astrocytes, and oligodendrocytes, are key players in the pathophysiology of ischemic stroke. Activated microglia and reactive astrocytes initiate and maintain an inflammatory response immediately after injury by producing proinflammatory cytokines and chemokines, thereby worsening neuronal damage and disrupting normal brain homeostasis. In the late stages of ischemic stroke, glial cells play a major role in neuroprotection, regeneration, and repair of damaged neuronal tissue by providing metabolic support to neurons, removing cellular debris, producing various neurotrophic and growth factors that support the survival of neurons, assisting the remodeling of axonal connections (synapses), promoting the regrowth of axons, and restoring normal function. Vagus Nerve Stimulation (VNS) has recently been developed as a neuroprotective intervention for ischemic stroke owing to its modulatory effects on neuroinflammation and neural plasticity. However, the precise molecular mechanism by which VNS regulates glial cell activity under ischemic conditions has not yet been fully elucidated. VNS may lead to the secretion of various cytokines, facilitate communication between glial cells, activate downstream signaling pathways, and promote neuroprotection following ischemic stroke. A more comprehensive understanding of these molecular pathways will lay a foundation for VNS-mediated neuroprotection and refine its future use in treating patients with stroke.