Knowledge of the mechanisms that trigger infection-related encephalopathies is still very limited and cell therapies are one of the most promising alternatives for neurodegenerative diseases, and its application in infectious diseases can be of great relevance. Mesenchymal stromal cells are cells with great immunomodulatory potential; therefore, their use in clinical and preclinical studies in a variety of diseases, including central nervous system diseases, increased in the last decade. Mesenchymal stromal cells can exert their beneficial effects through several mechanisms, such as direct cell contact, through surface receptors, and also through paracrine or endocrine mechanisms. The paracrine mechanism is widely accepted by the scientific community and involves the release of soluble factors, which include cytokines, chemokines and trophic factors, and extracellular vesicles. This mini review discusses mesenchymal stromal cells mechanisms of action in neurological disorders, the neuroinflammatory process that takes place in the brain as a result of peripheral inflammation and changes in the brain’s cellular scenario as a common factor in central nervous system diseases, and mesenchymal stromal cells therapy in encephalopathies. Mesenchymal stromal cells have been shown to act in neuroinflammation processes, leading to improved survival and mitigating behavioral damage. More recently, these cells have been tested in preclinical models of infectious diseases-associated encephalopathies (e.g., cerebral malaria and sepsis associated encephalopathy) and have shown satisfactory results.

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