Multicellular Exosomes as Therapeutic Modulators of Neuroinflammation: Mechanisms and Clinical Prospects.

Neuroinflammation is a fundamental pathological driver of diverse central nervous system (CNS) disorders, including Alzheimer's disease, stroke, and traumatic brain injury. This complex process is characterized by persistent neuronal damage and the orchestrated response of glial and peripheral immune cells. Intercellular communication during these inflammatory responses is increasingly attributed to exosomes, 30-150 nanometer (nm) extracellular vesicles that deliver bioactive lipids, proteins, and nucleic acids. These vesicles, secreted by neurons, glia, and mesenchymal stem cells, facilitate the sophisticated signaling networks necessary for maintaining neural homeostasis and immune regulation. However, while the individual roles of these vesicles are emerging, a comprehensive synthesis of how multicellular exosomal crosstalk collectively modulates the neuroinflammatory landscape remains elusive. This review systematically evaluates the bidirectional exchange of exosomes among diverse CNS cell populations and their specific roles in regulating inflammatory cytokine expression and immune cell phenotypes. We further examine the molecular mechanisms through which exosomal cargoes promote neural repair, alongside a critical analysis of current challenges in isolation, targeted delivery, and safety. By integrating these multicellular perspectives, this review provides a theoretical framework for utilizing exosomes as precision therapeutic modulators. Ultimately, it highlights the potential of exosome-based interventions to transform clinical outcomes for neuroinflammatory diseases.