Fig. 3
Adapted from Träger and Tabrizi [96]
A schematic depicting routes by which the peripheral immune activation influences neurodegeneration. (1) Mediators of peripheral inflammation and cells are permeable to the brain through circumventricular organs deficient of BBB. (2) Some selected immune mediators, like IL-6, are transported actively across the BBB. (3) Also immune mediators such as IL-1β can result to brain endothelium activation, thereby secreting nitric oxide, cytokines and immunological mediators into the brain. (4) Peripheral immune cells penetrate the brain either directly via the BBB, through the CSF (choroid plexus), thus contributing neurodegeneration. However, it is still unclear the extent to which cells can cross the BBB in neurodegeneration. (5) Finally, peripheral inflammation is translated into the brain through the vagus nerve in the neural reflex which coordinates systemic inflammation by sensing and inhibiting pro-inflammatory markers.