Introduction:
Subarachnoid hemorrhage (SAH) is a catastrophic event with high morbidity and a poor prognosis. To prevent SAH, its pathogenesis must be understood. Dental infection may play a part in the pathophysiology of intracranial aneurysms. In our newly established rat model of aneurysms, the vascular inflammatory response was associated with their rupture. Therefore we hypothesized that the inflammatory response exacerbated by periodontal pathogens affects experimental cerebral aneurysm rupture.
Methods:
Aneurysms were induced in 10-week-old female Sprague-Dawley rats by eliciting estrogen deficiency, renal hypertension, and hemodynamic stress. Two weeks later they were divided into 2 groups; group 1 (n=13) was treated with Porphyromonas gingivalis lipopolysaccharide (LPS), group 2 (n=17) was the saline control. Both groups were intraperitoneally injected once a week.
Results:
During the 90-day observation period, 7 group 1 (54%) and 6 group 2 rats (35%) suffered aneurysmal rupture. The incidence of rupture within 60 days was significantly higher in group 1 than group 2 (38% vs 6%, p<0.05), indicating that LPS promoted experimental aneurysmal rupture. The administration of LPS increased the plasma level of IL-1β and MMP-9 and the mRNA level of TLR2, IL-1β, and MMP-9 in the vascular wall prone to rupture on day 60. In our
in vitro
studies, IL-1β mRNA was increased in vascular smooth muscle cells exposed to LPS. These results suggest that LPS enhances the rupture of intracranial aneurysms via the promotion of local and systemic pro-inflammatory responses.
Conclusion:
Our study first documents that in rats, Porphyromonas gingivalis LPS exacerbates vascular inflammation and enhances the rupture of intracranial aneurysms.
Infection of microglia with Porphyromonas gingivalis promotes cell migration and an inflammatory response through the gingipain-mediated activation of protease-activated receptor-2 in mice