**7. Ischemic Stroke**

Epidemiological studies also sugges<sup>t</sup> an association between periodontitis and ischemic stroke. Stroke is the second most common cause of mortality worldwide and approximately 80% of strokes are caused by focal cerebral ischemia [76]. A recent meta-analysis [76] has shown a significant association between periodontitis and ischemic stroke based on three cohort studies [77–79] (pooled RR 2.52, 95% CI 1.77–3.58) and five case-control studies (pooled RR 3.04, 95% CI 1.10–8.43) [80–84]. Chi et al. (2019) examined mice with both experimental periodontitis induced by periodontal injection of LPS and photothrombotic ischemia. The study has demonstrated that chronic periodontitis exacerbates ischemic stroke through increasing the activation of microglia/astrocytes and the expression of nod-like receptor protein 3 inflammasome and IL-1β [85], suggesting that chronic periodontitis is a driving force for neuroinflammation associated with ischemia.
