Semanur GUNER, Elif Beyzanur POLAT, Humeysa KIYAK-KIRMACI, Hatice Kubra ELCIOGLU
Journal of Research in Pharmacy - 2026;30(4):1140-1147
Neuroinflammation plays a central role in the pathogenesis of various neurological disorders, with microglia serving as the primary immune regulators of the central nervous system. Depending on their activation state and phenotypic profile, microglia can exert either neurotoxic or neuroprotective effects. Citicoline, a well-established neuroprotective agent, has been increasingly investigated for its potential immunomodulatory effects; however, its specific impact on microglial activation and phenotypic polarization remains insufficiently characterized. This mini-review synthesizes findings from 12 experimental and clinical studies -including 10 in vivo studies across models of ischemic stroke, traumatic brain injury, epilepsy, hypoglycemia, demyelination, and Alzheimer's disease, one in vitro study using BV2 microglial cells, and one clinical study - identified through a comprehensive literature search. Citicoline was found to reduce pro-inflammatory mediators such as TNF-alpha, IL-1beta, and IL-6, while increasing anti-inflammatory markers such as IL-10 in several models. A subset of studies reported decreased expression of M1-associated markers and increased expression of M2-associated markers, suggesting a potential shift toward a neuroprotective microglial phenotype. However, findings remain heterogeneous across studies, largely due to differences in experimental models, treatment protocols, and outcome measures. It also remains unclear whether the observed effects reflect direct modulation of microglial cells or indirect effects mediated through the broader neuroinflammatory microenvironment. The current evidence supports a potential role for citicoline in modulating microglial phenotype; however, targeted, cell-specific experimental approaches are needed to elucidate the underlying mechanisms and inform the development of microglia-targeted therapeutic strategies.
