Mario García-Domínguez
Neuroinflammation is a defining feature of many neurological disorders, including neurodegenerative diseases, traumatic brain injury, and demyelinating conditions. Glial cells play a central role in this process by initiating, modulating, and resolving inflammatory responses in the CNS. This review examines the diverse roles of glial cells in neuroinflammation, focusing on their molecular and cellular interactions, context-dependent activation states, and phenotypic plasticity. It discusses how microglial activation can result in both neuroprotective and neurotoxic effects, while astrocytes contribute to immune regulation, blood-brain barrier integrity, and neuronal survival. The review also highlights interactions between glial cells and peripheral immune components, which may exert synergistic or antagonistic effects. Finally, it outlines emerging preclinical and clinical strategies targeting glial pathways to modulate several neuroinflammatory outcomes, emphasizing that a detailed understanding of glial dynamics is essential for developing effective CNS therapies.