Periapical lesion following Cnm-positive Streptococcus mutans pulp infection worsens cerebral hemorrhage onset in an SHRSP rat model

In this study, a dental pulp infection model with Streptococcus mutansin stroke-prone spontaneously hypertensive rats was established the progression of cerebral hemorrhage was observed. The localization of S. mutans-derived protein was observed in the vicinity of disrupted blood vessels. KSM153 WT (cnm-positive) and KSM153-cnm knockout induced similar antibody titers against S. mutans. However, the KSM153 WT strain caused more severe neurological symptoms and higher cerebral hemorrhage scores in the brain tissue than the KSM153 cnm mutant. Furthermore, the serum level of IL-1 beta increased significantly after infection with KSM153 WT. Cerebral hemorrhage severely affects the daily life of affected individuals. Streptococcus mutans and its adhesion factor Cnm increase the adverse effects of cerebral hemorrhages. However, the mechanism by which Cnm-positive bacteria migrate from apical lesions to cerebral hemorrhage sites is unclear. Therefore, we established an S. mutans-infected apical lesion in a rat model of hypertension and investigated the neurological symptoms associated with cerebral hemorrhage. Eighteen 12-week-old stroke-prone spontaneously hypertensive rats were randomly divided into three groups, i.e. the no infection (control), dental infection with S. mutans KSM153 wild type (Cnm positive), and KSM153 Delta cnm groups. Immunofluorescent staining was performed to visualize S. mutans protein. Serum interleukin-1 beta levels were measured. The adhesion of S. mutans to the extracellular matrix and human fibroblast cells was also analyzed. Serum antibody titers against S. mutans were comparable between Cnm positive and knockout mutants. However, 3-10 days post-infection, neurological symptom scores and cerebral hemorrhage scores were higher in Cnm-positive rats than in knockout mutants. The localization of S. mutans-derived protein was observed in the vicinity of disrupted blood vessels. Serum interleukin-1 beta levels significantly increased post-KSM153 WT infection. Cnm-positive S. mutans clinical isolates showed increased adhesion to the extracellular matrix, human dental pulp cells, and human umbilical vein endothelial cells compared with the Cnm-negative S. mutans isolates. In conclusion, Cnm-positive bacteria colonize the apical lesion site using the extracellular matrix as a foothold and affect cerebral hemorrhage via the bloodstream.