gms | German Medical Science

Chronic peripheral inflammation is present in rheumatoid arthritis and frequently associated with neuropsychiatric comorbidities like depression and cognitive impairment. The CNS comorbidity is generally explained by inflammatory spreading of signal molecules and/or immune cells from the periphery into the brain, resulting in neuroinflammation and subsequent structural and functional damages within the CNS. However, it is not well understood which mechanisms mediate immune propagation into the CNS and, more importantly, whether different brain regions show a distinct vulnerability towards peripheral inflammatory stimuli. We investigated the regional specificity of cellular immune invasion into the brain using human TNF-α overexpressing (hTNFtg) mice, a well-established model for rheumatoid arthritis characterized by severe innate peripheral inflammation. Immunohistochemical analysis revealed an increased presence of CD45+ peripheral leukocytes in the cortex, thalamus, and striatum of 12-week-old hTNFtg mice, whereas there was no increase in CD45+ cells in the hippocampus and the cerebellum. This finding is in line with our previous study showing preservation of hippocampal immune state and function in hTNFtg mice. Region-specific presence of peripheral immune cells indicates a rather topographical selectivity of immune-to-brain communication in a state of chronic innate peripheral inflammation. Further analysis of the regional inflammatory milieu as well as the mechanism allowing CD45+ cells to cross the blood-brain barrier will provide new insights in inflammatory propagation from the periphery to the CNS and might contribute to the understanding of neuropsychiatric comorbidity in chronic peripheral inflammatory disease.