Endodontic Treatment of Apical Periodontitis Mitigates Systemic Inflammation and Restores the Blood–Brain Barrier Integrity in an In Vitro Model
Loredana Bergandi, Mario Alovisi, Elena Tachis, Nicola Scotti, Andrea Baldi, Iris Chiara Salaroglio, Sabrina Digiovanni, Lorena Charrier, Francesca Silvagno, Damiano PasqualiniABSTRACT
Aim
A growing body of research supports an association between periapical inflammation and an increased risk of various systemic effects. However, there is currently no scientific evidence demonstrating a causal relationship between this inflammation and changes in epithelial or endothelial permeability in patients with apical periodontitis (AP). This study aimed to evaluate the potential association between AP, circulating inflammatory cytokines known to affect cellular permeability, and serum proteins associated with an impaired cellular barrier permeability. Additionally, we investigated the effect of endodontic treatment on in vitro endothelial barrier integrity.
Methodology
A total of 27 patients with AP and 27 healthy control subjects were enrolled. AP patients underwent root canal treatment and were followed up at 6 and 12 months post‐treatment. Serum levels of human ZO‐1, Claudin‐5, and VE‐cadherin were measured using enzyme‐linked immunosorbent assays (ELISA). An in vitro model of the microvascular endothelial blood–brain barrier (hCMEC/D3 cells) was used to assess the biological activity of patient sera on barrier function and cellular permeability.
Results
At baseline, patients with AP showed significantly higher serum levels of ZO‐1 and Claudin‐5 compared with controls ( p < 0.001), whereas VE‐cadherin levels did not differ significantly between groups. Serum ZO‐1 and Claudin‐5 levels progressively decreased at 6 and 12 months following root canal treatment. In adjusted analyses, the baseline between‐group differences for ZO‐1 and Claudin‐5 remained significant after adjustment for BMI and smoking status. ZO‐1 and Claudin‐5 levels showed moderate correlations with IL‐1β and IL‐6 in the AP group at baseline. In vitro, exposure to baseline AP sera increased endothelial permeability, indicating barrier disruption, while sera collected after treatment did not impair barrier integrity. Moreover, cellular ZO‐1 expression remained stable in cells treated with control sera but was markedly reduced after exposure to sera from untreated AP patients (t0), whereas post‐treatment sera (t6 and t12) restored ZO‐1 expression to control levels.
Conclusions
Systemic inflammation in patients with apical periodontitis to deranged endothelial barrier function. Successful endodontic treatment was associated with reduced levels of inflammatory cytokines and the restoration of serum and cellular proteins essential for barrier integrity.