Unveiling the Impact of Porphyromonas gingivalis-Associated Periodontitis on Stroke Outcome in Mice

Abstract

BACKGROUND: Periodontitis is a chronic inflammatory condition with infectious origin that affects the tissues supporting the teeth. Increasing epidemiological evidence suggests that periodontitis is a risk factor for ischemic stroke with associated adverse outcomes. However, the underlying mechanism of this association remains incompletely elucidated. METHODS: We used a C57BL/6J mice model of ischemic stroke induced by transitory occlusion of the middle cerebral artery in the presence or absence of ligature-induced periodontitis using Porphyromonas gingivalis-soaked ligatures. Stroke severity was evaluated through infarct volume, sensorimotor deficit, blood-brain barrier (BBB) integrity, and markers of systemic and brain inflammation. The direct effect of P gingivalis on BBB endothelial cells was further explored in vitro. RESULTS: Mice with P gingivalis-associated periodontitis showed a significant exacerbation of stroke severity: larger infarct volume, more severe sensorimotor deficit, greater BBB disruption, and increased brain neutrophil infiltration compared with sham. Systemic inflammation was also markedly elevated. Intravenous administration of P gingivalis alone, without gingival injury, before transitory occlusion of the middle cerebral artery was sufficient to amplify brain inflammation and stroke lesions. In vitro P gingivalis, through its gingipain proteases, directly impaired BBB integrity by increasing endothelial permeability and disrupting tight-junction proteins. CONCLUSIONS: Our findings demonstrate that P gingivalis-associated periodontitis worsens ischemic stroke outcome both indirectly by enhancing systemic and brain inflammation and directly via BBB disruption. These results highlight periodontitis as a modifiable risk factor and potential therapeutic target for improving stroke prognosis.