LOSARTAN PROTECTS HIPPOCAMPAL NEUROVASCULAR UNITS BY PRESERVING BARRIER INTEGRITY AND REDUCING REACTIVE GLIOSIS IN DEXTRAN SODIUM SULFATE-INDUCED COLITIS

Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, are characterized by chronic systemic inflammation. Emerging evidence indicates that chronic systemic inflammation induced by colitis is associated with a high risk to develop cognitive impairment and brain disorders including anxiety and mood disorders. We hypothesized that colitis-induced BBB disruption might be a culprit to underlie such gut-brain axis. In the present study, we have investigated whether colitis-induced alteration in the brain can be rescued by losartan, an FDA-approved antihypertensive drug that is previously known to ameliorate BBB-induced neural dysfunction. We have found that losartan preserved BBB integrity in the DSS-induced colitis mouse model. Losartan treatment restored the expression of Claudin-5, a tight junction protein abundantly expressed on brain endothelial cells. It also suppressed the pathological activation of astrocytes and microglia induced by colitis. These findings suggest that losartan has a therapeutic potential against DSS-induced colitis with respect to the BBB integrity and reactive glia.