Beyond OPCs: Electroacupuncture-Associated Glial Network Modulation as a Testable Hypothesis for Remyelination and Neuroregeneration

Remyelination is often described as an oligodendrocyte precursor cell (OPC)-driven process, yet successful repair depends on a multicellular lesion environment that includes microglia, astrocytes, neurons, vascular elements and infiltrating immune cells. Our previous preprint proposed that acupuncture-associated adenosinergic signaling may modulate OPC differentiation and remyelination in a receptor-, stage- and lesion-context-dependent manner. The present article expands that model without assuming that local adenosine directly reaches a demyelinated central nervous system (CNS) lesion or that a single glial cell type initiates repair. We propose that electroacupuncture may generate at least two partially independent peripheral inputs: a local purinergic response and site- and intensity-dependent somatosensory-autonomic reflexes. Through an unresolved peripheral-to-lesion bridge, these inputs may alter neural, humoral and immune mediators that influence the cellular state of demyelinated tissue. We define glial network remodeling as coordinated, time-dependent changes in microglial debris clearance and lipid handling, astrocytic metabolic and extracellular-environmental support, neuroimmune signaling and oligodendrocyte-lineage progression that collectively change lesion permissiveness for remyelination. This formulation does not impose a universal microglia-to-astrocyte-to-OPC sequence; instead, it predicts causal interdependence among glial populations and explicitly allows disease-, phase- and stimulation-specific variation. The framework is a preclinical mechanistic hypothesis, not a claim that electroacupuncture is an established remyelinating treatment.