Expression of the Tight Junction Protein Claudin in the Blood-Brain Barrier in the Temporal Lobe of Patients with Drug-Resistant Epilepsy

Epilepsy is a major global health issue, and despite the availability of antiepileptic drugs, more than 30% of patients develop drug-resistant epilepsy and require surgical treatment. It is now known that disruption of the blood-brain barrier (BBB) is one of the manifestations of this disease, and in animal studies, the severity of epileptic seizures correlates with the degree of BBB disruption. Changes in the tight junctions of endothelial cells, specifically in the amount of claudin protein, which is a key component of the BBB, are of great interest. The purpose of this study was to investigate claudin immunoreactivity in the cerebral cortex and white matter of patients with drug-resistant epilepsy (DRE). Materials and Methods: Biopsy material from fragments of the temporal lobe was obtained intraoperatively from 15 patients (5 women, 10 men) with locally-caused DRE, aged 20 to 42 years with an average age of 28.7 years. Autopsy material from 6 patients who died from somatic diseases and had no history of neurological disorders was used as a comparison group. Histological sections stained with hematoxylin and eosin, as well as immunohistochemical (IHC) reactions with antibodies to claudin, were studied. The results of the IHC reactions were assessed by calculating the densitometric density of stained basement membranes of vessels in 10 fields of view of the cortex and white matter of the resected temporal lobe in each patient. Statistical analysis was carried out using the Statistica v.10 program, and a difference was considered significant at p<0.05. Results: Histological analysis revealed focal cortical dysplasia in all patients. IHC reactions with claudin showed varying degrees of immunopositivity in the vascular endothelium of patients with DRE, with some cases showing complete loss of claudin. In the cortex, the level of claudin expression ranged from 0.072 to 0.554 (mean = 0.267 ± 0.088), and in the white matter, it ranged from 0.048 to 0.528 (mean = 0.181 ± 0.064). Statistical analysis showed no significant difference in claudin expression between patients with drug-resistant epilepsy and the comparison group (p-value = 0.43). However, a significant difference was found in the cortex according to the Mann-Whitney U test (p-value = 0.01). A correlation analysis using Spearman's correlation coefficient revealed a medium-strength negative correlation. Conclusion: In patients with drug-resistant epilepsy, there is a decrease in claudin-5 immunoreactivity in the cerebral cortex. Defects in tight junction proteins, with a predominant effect on cortical vessels, may be both a primary and secondary factor in epilepsy and could potentially be a therapeutic target in this group of patient.