Unveiling the Impact of-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-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 ofon BBB endothelial cells was further explored in vitro. RESULTS: Mice with-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 ofalone, without gingival injury, before transitory occlusion of the middle cerebral artery was sufficient to amplify brain inflammation and stroke lesions. In vitrothrough its gingipain proteases, directly impaired BBB integrity by increasing endothelial permeability and disrupting tight-junction proteins. CONCLUSIONS: Our findings demonstrate that-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.