Neuroinflammatory Dysfunction of the Blood–Brain Barrier and Basement Membrane Dysplasia Play a Role in the Development of Drug-Resistant Epilepsy

Author:

Zabrodskaya Yulia1,Paramonova Natalia23,Litovchenko Anastasia2ORCID,Bazhanova Elena24ORCID,Gerasimov Aleksandr1ORCID,Sitovskaya Darya1ORCID,Nezdorovina Victoria1,Kravtsova Svetlana1,Malyshev Stanislav1,Skiteva Ekaterina15,Samochernykh Konstantin1

Affiliation:

1. Polenov Neurosurgical Institute—Branch of the Almazov National Medical Research Centre, 197341 St. Petersburg, Russia

2. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 St. Petersburg, Russia

3. State Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation, 195043 St. Petersburg, Russia

4. Golikov Research Center of Toxicology, 192019 St. Petersburg, Russia

5. State Scientific Center of the Russian Federation, Institute of Biomedical Problems of the Russian Academy of Sciences, 123007 Moscow, Russia

Abstract

Drug-resistance epilepsy (DRE) is a key problem in neurology. It is possible that damage to the blood–brain barrier (BBB) may affect resistance in DRE. The aim of this work was to assess the damage and dysfunction in the BBB in the area of epileptic foci in patients with DRE under conditions of neuroinflammation. The changes to the BBB in temporal lobe epilepsy (by immunohistochemistry and transmission electron microscopy), levels of neuroinflammatory proteins, and cytokine levels in the blood (by multiplex analysis) were studied. Increased levels of vascular endothelial growth factor (VEGF) and growth-regulated protein (GRO), and decreased levels of epidermal growth factor (EGF) in plasma, combined with overexpression of the VEGF-A receptor by endotheliocytes were detected. Malformation-like growths of the basement membrane of the capillaries of the brain complicate the delivery of antiepileptic drugs (AEDs). Dysplasia of the basement membrane is the result of inadequate reparative processes in chronic inflammation. In conclusion, it should be noted that damage to the microcirculatory network of the brain should be considered one of the leading factors contributing to DRE.

Funder

Ministry of Health of the Russian Federation to the ANMRC

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference47 articles.

1. Karlov, V.A. (2019). Epilepsy in Children and Adults, Women and Men, BINOM. [2nd ed.].

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3. Mechanisms of Action of Currently Used Antiseizure Drugs;Sills;Neuropharmacology,2020

4. Antiepileptic drugs in critically ill patients;Farrokh;Crit. Care,2018

5. Efficacy and safety of dibufelon in drug-resistant epilepsy;Ivanova;Ross. Neirokhirurgicheskii Zhurnal Im. Profr. A.L. Polenova,2023

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