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. Author manuscript; available in PMC: 2015 Oct 7.
Published in final edited form as: Lancet Psychiatry. 2015 Feb 25;2(3):258–270. doi: 10.1016/S2215-0366(14)00122-9

Figure 1. How peripheral immune signals reach the brain to contribute to neuropsychiatric symptoms.

Figure 1

(A) Neural pathway: peripheral cytokines activate the vagus nerve, and the signal reaches brain nuclei by retrograde axonal transport. (B) Humoral pathway: panel on right shows macrophage-like cells residing in the CVOs and the CP responding to circulating PAMPs by producing cytokines which enter the brain by volume diffusion. Panel on left shows that inflammation activates cerebral vascular endothelial cells. This leads to increased transmigration of monocytes into the brain, and activation of microglia and perivascular macrophages. All of these cells release proinflammatory cytokines in the brain. Adapted with permission from Dantzer and colleagues.1 NTS=nucleus tractus solitarius. VLM=ventrolateral medulla. CEA=central amygdala. PVN=periventricular nucleus. SON=supraoptic nucleus. PB=parabrachial nucleus. PAG=periaqueductal grey. BNST=bed nucleus for stria terminalis. CP=choroid plexus. TLR=Toll-like receptor. PAMP=pathogen-associated molecular patterns. CVO=circumventricular organ. PVM=peri-vascular macrophage.