Blood‐brain barrier injury during spirochetal infection

Abstract

The most severe and a relatively common complication of untreated relapsing fever (RF) borreliosis is brain hemorrhage; mortality rate can reach as high as 70% in the epidemic form. Subjects with epidemic RF who are stable prior to treatment have extraordinarily high levels of circulating IL‐10. Our studies in murine RF borreliosis have shown that IL‐10 protects the microcirculation of the brain and others organs from hemorrhagic and thrombotic complications. Mortality is higher in infected mice deficient only in IL‐10 compared to mice normal for IL‐10 but deficient in both B and T cells. In this study we examined morphologically and molecularly the brain of mice with relapsing‐remitting and persistent infection with B. turicatae (Bt) with or without IL‐10 deficiency for alterations in the BBB. The analysis shows significant BBB disruption in IL‐10 deficient infected mice often resulting in brain hemorrhage. Immufluorescence microscopy of vessels near hemorrhagic areas shows rupture of basal lamina, detachment of astrocytes foot processes and pericytes, leakage of serum proteins, decreased in tight junction proteins, endothelial cell activation and apoptosis, and recruitment of inflammatory cells. These results indicate that IL‐10 protects the BBB at multiple levels during spirochetal infection to prevent injury. Studies funded by NIH grant R21 NS057545‐02 to Diego Cadavid.