Figure 1.

Schematic of the putative mechanisms of action of mesenchymal stem cell (MSC) therapy in neurological diseases. (A) Neurological challenges, such as infections, head trauma, and autoimmune diseases, may lead to brain injury, characterized by a release of proinflammatory cytokine. However, even peripheral organ damage may upregulate the levels of proinflammatory cytokines in circulating blood, finally reaching the brain throughout systemic circulation. Once circulating cytokines interact with a neuro-vascular unit, the neuronal excitability threshold is lower and electrical paroxysmal events may happen, leading to a possible alteration of the local neuronal circuitry. (B) When MSCs are administered peripherally, (C) a smaller part is directly mobilized to the site of injury, while (D) most cells get trapped in organs such as the liver, lungs, lymph nodes, and spleen. (E) Here, MSCs are activated by inflammatory mediators and release paracrine factors and microvesicles in the bloodstream. (F) These molecules reach the site of injury, and, together with MSCs previously recruited, modulate the progression of inflammation and facilitate tissue repair.