Apical Periodontitis and Blood–Brain Barrier Compromise: Biological Mechanisms and Current Evidence—A Narrative Review
5 affiliations
- 1Department of Comprehensive Adult Dentistry, Oral Biology Research Center, Faculty of Dentistry, Universidad de La Frontera, Temuco 4811230, Chile
- 2Department of Oral Pathology and Medicine, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
- 3Department of Periodontics, Faculty of Dentistry, Universidad de los Andes, Santiago 7550000, Chile
- 4Department of Pathology and Experimental Therapy, Facultat de Medicina, Universitat de Barcelona, 08907 L’Hospitalet de Llobregat, Spain
- 5Department of Conservative Dentistry, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
Abstract
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.
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BibTeX
@article{bucchi2026apical,
title = {{Apical Periodontitis and Blood–Brain Barrier Compromise: Biological Mechanisms and Current Evidence—A Narrative Review}},
author = {Cristina Bucchi and Marcela Hernández and Alejandra Chaparro and Josep Maria de Anta and María José Bordagaray},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219594},
url = {https://www.mdpi.com/1422-0067/27/21/9594},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Apical Periodontitis and Blood–Brain Barrier Compromise: Biological Mechanisms and Current Evidence—A Narrative Review
AU - Cristina Bucchi
AU - Marcela Hernández
AU - Alejandra Chaparro
AU - Josep Maria de Anta
AU - María José Bordagaray
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219594
UR - https://www.mdpi.com/1422-0067/27/21/9594
AB - 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.
SN - 1422-0067
ER -