Profiling Tight Junction Protein Expression in Brain Vascular Malformations.

1. Int J Mol Sci. 2025 May 9;26(10):4558. doi: 10.3390/ijms26104558. Profiling Tight Junction Protein Expression in Brain Vascular Malformations. Pedrosa L(1)(2), Mosteiro A(3), Reyes L(3), Amaro S(1)(2)(4), Menéndez-Girón S(5), Rivera MC(5), Domínguez CJ(5), Planas AM(1)(6), Torné R(1)(2)(3), Rodríguez-Hernández A(5). Author information: (1)August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain. (2)Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain. (3)Department of Neurosurgery, Institute of Neuroscience, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. (4)Comprehensive Stroke Center, Institute of Neuroscience, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. (5)Department of Neurosurgery, Germans Trias i Pujol University Hospital, Carretera de Canyet, s/n, 08916 Badalona, Spain. (6)Department of Neuroscience and Experimental Therapeutics, Institute for Biomedical Research of Barcelona (IIBB), Spanish Research Council (CSIC), 08036 Barcelona, Spain. Recent studies suggest that blood-brain barrier (BBB) disruption plays a key role in the clinical course and bleeding risk of brain arteriovenous malformations (bAVMs). The tight junctions (TJs) are complex endothelial transmembrane proteins with a significant physical contribution to BBB disruption. In this study, we hypothesized that bAVMs display a different TJ pattern than other vascular malformations and normal brain tissue. We studied the expression of claudin-5 and occludin as essential factors for functional TJs. Human specimens of surgically resected cavernomas (CCMs) (n = 9), bAVMs (n = 17), and perilesional brain parenchyma (6 from CCMs and 16 from bAVM patients) were analyzed via immunofluorescence staining, transmission electron microscopy (TEM), and Western blot tests. Compared to perilesional parenchyma, bAVMs showed a significant decrease in TJ protein expression, and these alterations were more apparent in ruptured bAVMs than in unruptured bAVMs or CCMs. TEM images provided evidence of disrupted connectivity between endothelial cells of bAVMs. This is the first clinical investigation that studies the expression of TJs in human bAVMs and their surrounding parenchyma. Despite the limitations of the sample size, we found significant differences in the expression and composition of TJs in bAVMs when compared to surrounding parenchyma and other vascular lesions such as CCMs. These results add further evidence to the role of BBB disruption in the clinical course of bAVM. A deeper understanding of these mechanisms may lead to the development of new therapeutic targets and management strategies for bAVMs. DOI: 10.3390/ijms26104558 PMCID: PMC12111537 PMID: 40429705 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.