Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 20, Pages -Publisher
MDPI
DOI: 10.3390/ijms232012561
Keywords
drug-resistant epilepsy; apoptosis; neuroinflammation; cytokines; neurons; glia
Funding
- Russian Foundation for Basic Research (RFBR) [20-015-00127]
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This study evaluated neuronal and glial apoptosis in the brain epileptic focus and inflammatory changes in the blood in patients with focal drug-resistant epilepsy. The results showed signs of apoptosis in neurons and oligodendrocytes in the temporal lobe of DRE patients. Increased levels of proinflammatory cytokines and decreased levels of anti-inflammatory cytokines were observed. Oligodendroglial apoptosis was found to play an important role in DRE pathogenesis and explain demyelination.
Neuroglial apoptosis and neuroinflammation play an important role in epileptogenesis. The aim of this study is to evaluate neuronal and glial apoptosis in association with neuroinflammation in brain epileptic focus and inflammatory changes in blood in patients with focal drug-resistant epilepsy (DRE). Pathological changes in the temporal lobe in epilepsy (histology, transmission electron microscopy), levels of apoptotic and neuroinflammatory proteins: active caspase-3 (immunohistochemistry), full-length form caspase-3, caspase-9, FAS, FAS-L, NF-kB, TNF-alpha, p53 (Western blot), and cytokine levels in blood: IL-1 beta, IL-2, IL-4, IL-7, TNF-alpha, etc. (multiplex analysis) were studied. In the present work, ultrastructural and immunohistochemical apoptotic signs were found in neurons and oligodendrocytes in the temporal lobe of DRE patients. Levels of proinflammatory cytokines that play a role in apoptosis (TNF-alpha, FAS, NF-kB) were increased. The blood concentration of IL-4, IL-7, TNF-alpha is increased and IL-2 is reduced. Oligodendroglial apoptosis has been shown to play an important role in DRE pathogenesis and to explain demyelination. Thus, a comprehensive analysis of revealed changes in the blood and brain in DRE patients showed the neuroinflammation in the epileptic focus, which was combined with the development of apoptosis of glial cells and neurons. This creates conditions for the development of drug resistance and the epilepsy progression.
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