Abstract
Increasing evidence hints to the central role of neuroinflammation in the development of post-stroke depression. Danger signals released in the acute phase of ischemia trigger microglial activation, along with the infiltration of neutrophils and macrophages. The increased secretion of proinflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNFα) provokes neuronal degeneration and apoptosis, whereas IL-6, interferon γ (IFNγ), and TNFα induce aberrant tryptophane degradation with the accumulation of the end-product quinolinic acid in resident glial cells. This promotes glutamate excitotoxicity via hyperexcitation of N-methyl-D-aspartate receptors and antagonizes 5-hydroxy-tryptamine, reducing synaptic plasticity and neuronal survival, thus favoring depression. In the post-stroke period, CX3CL1 and the CD200-CD200R interaction mediates the activation of glial cells, whereas CCL-2 attracts infiltrating macrophages. CD206 positive cells grant the removal of excessive danger signals; the high number of regulatory T cells, IL-4, IL-10, transforming growth factor β (TGFβ), and intracellular signaling via cAMP response element-binding protein (CREB) support the M2 type differentiation. In favorable conditions, these cells may exert efficient clearance, mediate tissue repair, and might be essential players in the downregulation of molecular pathways that promote post-stroke depression.