Journal of the American Heart Association · 2025
Unveiling the Impact of Porphyromonas gingivalis-Associated Periodontitis on Stroke Outcome in Mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Diallo Devy, Mangin Gabrielle, Cheat Banndith, Even Guillaume, Gaston Anh-Thu, Bouchet Jérome, Desilles Jean-Philippe, Clement Marc, Nicoletti Antonino, Caligiuri Giuseppina, Gosset Marjolaine, Delbosc Sandrine
Аннотация
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.
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.