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

被引:7
作者
Zabrodskaya, Yulia [1 ]
Paramonova, Natalia [2 ,3 ]
Litovchenko, Anastasia [2 ]
Bazhanova, Elena [2 ,4 ]
Gerasimov, Aleksandr [1 ]
Sitovskaya, Darya [1 ]
Nezdorovina, Victoria [1 ]
Kravtsova, Svetlana [1 ]
Malyshev, Stanislav [1 ]
Skiteva, Ekaterina [1 ,5 ]
Samochernykh, Konstantin [1 ]
机构
[1] Almazov Natl Med Res Ctr, Polenov Res Inst, St Petersburg 197341, Russia
[2] Russian Acad Sci, Sechenov Inst Evolutionary Physiol & Biochem, St Petersburg 194223, Russia
[3] Minist Def Russian Federat, State Res Testing Inst Mil Med, St Petersburg 195043, Russia
[4] Golikov Res Ctr Toxicol, St Petersburg 192019, Russia
[5] Russian Acad Sci, Inst Biomed Problems, State Sci Ctr Russian Federat, Moscow 123007, Russia
关键词
drug-resistant epilepsy; blood-brain barrier; neuroinflammation; cytokines; VEGF; basement membrane; dysplasia; immunohistochemistry; electron microscopy; multiplex analysis; IV; COLLAGEN; COL4A1; VEGF;
D O I
10.3390/ijms241612689
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:14
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