Неврология, нейропсихиатрия, психосоматика (Feb 2023)

Glioneuronal apoptosis and neuroinflammation in drug resistant temporal lobe epilepsy

  • T. V. Sokolova,
  • A. V. Litovchenko,
  • N. M. Paramonova,
  • V. R. Kasumov,
  • S. V. Kravtsova,
  • V. G. Nezdorovina,
  • D. A. Sitovskaya,
  • E. N. Skiteva,
  • E. D. Bazhanova,
  • Y. M. Zabrodskaya

DOI
https://doi.org/10.14412/2074-2711-2023-1-36-42
Journal volume & issue
Vol. 15, no. 1
pp. 36 – 42

Abstract

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The study of glioneuronal apoptosis and neuroinflammation is extremely important for understanding the causes of epilepsy. Currently, the focus is on neuronal apoptosis and certain aspects of neuroinflammation, while glial apoptosis remains poorly understood.Objective: to evaluate neuronal and glial apoptosis in conjunction with neuroinflammation in the area of the epileptic focus in patients with focal drug-resistant epilepsy (DRE).Material and methods. Biopsy specimens of the cortex and white matter of the temporal lobe of the brain from 30 patients with focal DRE due to focal cortical dysplasia were studied. We evaluated pathological changes and structural signs of apoptosis, levels of apoptotic and pro-inflam-matory factors such as caspase-3, caspase-9, FAS, FAS ligand (FAS-L), tumor necrosis factor α (TNFα), p53, nuclear factor κB (NF-κB). Histological methods, transmission electron microscopy (TEM), immunohistochemical study (IHC), and Western blot (WB) were used. The comparison group consisted of 21 people without epilepsy and brain involvement.Results. In DRE patients IHC revealed the expression of active caspase-3 in single neurons (20% of cases) and in gliocytes of the cerebral cortex and white matter (100% of cases). TEM revealed ultrastructural signs of apoptosis in all cases in neurons and oligodendrocytes. The WB of the epileptic focus showed an increased expression of the apoptotic factors caspase-9, FAS, p53 and pro-inflammatory factors TNFα, NF-κB.Conclusion. The results obtained indicate the presence of associated apoptosis and neuroinflammation processes of in DRE. Glial apoptosis is actively involved in epileptogenesis. The main part of apoptotic glia is oligodendrocytes, which explains the well-known phenomenon of myelin damage in epilepsy. Along with neuronal apoptosis, oligodendrocyte apoptosis together with neuroinflammation forms a self-sustaining pathological focus, which contributes to the progression of the disease and the occurrence of relapses.

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