The ARIC study confirmed an independent association between periodontal disease and incident ischemic stroke risk, particularly cardioembolic and thrombotic stroke subtypes [7]. serum CRP and serum IgG titers to each periodontal pathogen. Table 3 Univariate analysis of antibody titers to periodontal pathogens (positive for periodontal pathogens) to determine associations with unfavorable outcome. and numbers of IgG antibodies positive for periodontal pathogens were independent predictors of unfavorable outcome in ischemic stroke patients. The associations between periodontal disease and ischemic stroke have been reported in several studies. The first National Health and Nutrition Examination Survey showed that periodontal disease is one of the risk factors of ischemic stroke [16]. The ARIC study confirmed an independent association between periodontal disease and incident ischemic stroke risk, particularly cardioembolic and thrombotic stroke subtypes [7]. Furthermore, some cohort studies have reported that dental care or periodontal disease treatment could reduce the incidence of ischemic stroke [7, 17, 18]. On the other hand, the influence of periodontal disease on outcome of ischemic stroke patients has not been established. We revealed a significant association between serum IgG titers to periodontal pathogens and outcome of ischemic stroke patients. There is a possibility that regular dental care not only reduces the incidence of ischemic stroke, but also prevents severe neurological deficits in the acute phase of ischemic stroke. We used serum IgG titers to periodontal pathogens to investigate the association between periodontal disease and outcome of ischemic stroke. Circulating IgG levels against periodontal pathogens may be more accurate measures of periodontal infection and its severity in previous studies [19, 20]. There are several reports demonstrating the association between antibodies to periodontal pathogens and coronary heart disease [21C23]. However, there have been few studies investigating the association between antibodies to periodontal pathogens and ischemic stroke. Pussinen and are associated with incident stroke [24]. Hosomi antibody may be associated with atherothrombotic stroke [12]. We previously demonstrated that serum antibody titers to were independent predictors of unfavorable outcome in all subtypes of stroke patients [15]. elicits a variety of host responses, and is a potent stimulator of the inflammatory cytokines, IL-6, IL-8, and TNF [30, 31]. In the GSK1904529A present study, numbers of IgG antibodies positive for periodontal pathogens are independent predictors of unfavorable outcome in only ischemic stroke patients, not in hemorrhagic stroke patients. There is a possibility that an interaction between multiple periodontal pathogens may have negative effects GSK1904529A on acute infarction. However, whether periodontal disease can modify acute ischemic brain damage is not fully understood. OBoyle can compromise and cross the blood brain barrier into the brain [33], and spp. have been speculated to enter the brain directly via peripheral trigeminal GSK1904529A nerves [34]. is also reported to be able to pass through the blood-brain barrier and has been found to be causative of brain abscesses in some case studies [35, 36]. Multiple periodontal pathogens infections are considered to cause higher-grade systemic inflammation. Several reports showed that high-grade systemic inflammation is deleterious in the context of ischemic stroke [37C39]. We speculate GSK1904529A that this is a part of the reasons why numbers of IgG antibodies positive for periodontal pathogens are independent predictors of unfavorable outcome in ischemic stroke patients. Further studies are needed to clarify this point. There are some limitations to our study. First, we did not evaluate the oral conditions such as tooth loss and grade of periodontal disease, socioeconomic status, and access to dental care in each patient. We cannot eliminate the possibility that these factors can influence the outcome in ischemic stroke patients. However, several reports have shown that IgG levels against periodontal pathogens are more accurate measures of periodontal infection and its severity. Takeuchi et al. showed that higher anti-IgG levels were found in the periodontitis group compared with the healthy control group [40]. Pussinen et al. found that ELISA is suitable for measuring antibodies to periodontal pathogens in large epidemiological studies in order to evaluate the role of periodontitis as a risk ATP2A2 factor for other diseases [20]. Kudo et al. revealed that IgG titers of periodontitis patients were significantly higher than those of healthy controls, particularly in those with sites of probing depth over 4 mm [41]. In this way, IgG titers to periodontal pathogens are established as a surrogate marker of periodontal health. Moreover, we assessed the tooth status of 85 patients. The tooth status was evaluated by a dentist within 7 days after admission. The median numbers of remaining teeth were 23 (IQR 14C26), and treated teeth were 9 (IQR 4C14). Patients with unfavorable outcomes had significantly lower numbers of remaining teeth than patients with favorable outcomes. (20 [IQR 10C25] vs. 24 [IQR GSK1904529A 16C27], p = 0.03). We found a positive correlation between the numbers of teeth lost and the numbers of positive for periodontal pathogens. Therefore, we believe that this limitation does not have a substantial influence on.