Apical Periodontitis and Blood–Brain Barrier Compromise: Biological Mechanisms and Current Evidence—A Narrative Review

This narrative review explores the potential link and the associated biological mechanisms between apical periodontitis (AP) and blood–brain barrier (BBB) integrity. An electronic literature search to identify publications related to AP and BBB integrity was conducted using the Scopus and PubMed databases. Both experimental and clinical studies were included and qualitatively analyzed. Available evidence shows that serum inflammatory marker levels are elevated in patients with AP compared to healthy controls, including proteins associated with endothelial barrier disruption such as ZO-1 and Claudin-5. Indirect evidence shows that disruption of the BBB can occur due to circulating inflammatory cytokines and pathogen insults. BBB cells express receptors that respond to circulating insults by upregulating pro-inflammatory cytokines, necroptosis, and proteolytic activity, which compromise BBB integrity. Elevated baseline levels of inflammatory markers from other chronic oral diseases, particularly periodontitis, have been linked to an increased risk of neurological disorders. Although similar pathophysiological mechanisms may be involved and recent in vitro experimental evidence suggests that the systemic inflammatory milieu associated with AP may compromise BBB function, direct in vivo and clinical evidence establishing a causal link remains lacking. Although biological plausibility supports a role for AP in BBB disruption, and recent in vitro experimental evidence has provided the first preliminary support for this association, in vivo preclinical studies and prospective clinical longitudinal studies are still needed to establish a clear causal relationship. Given the global burden of neurological disorders, elucidating the potential impact of AP on BBB integrity represents an important avenue for research.