Apoptosis of Brain Cells in Epileptic Focus at Phapmacresistant Temporal Lobe Epilepsy

Соколова, Т. В.; Забродская, Ю.М.; Парамонова, Н. М.; Доброгорская, Л. Н.; Куралбаев, А. К.; Касумов, В. Р.; Ситовская, Д. А.

doi:10.18705/2311-4495-2017-4-6-22-33

Cited by 7 publications

(5 citation statements)

References 10 publications

(19 reference statements)

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“…In fact, astrocyte dysfunction has been proposed as a basis for epilepsy, as both animal models and human samples suggest that astrocytes play roles in hyperarousal, neurotoxicity, seizure spread, and other neurogenic functions [15,16]. Furthermore, oligodendrocytes play an important role in epileptogenesis and the development of degenerative processes in DRE [17]. This recognition has led the European Commission of the International League Against Epilepsy (ILAE) to identify glial and inflammatory mechanisms in seizure development and epileptogenesis as a top research priorities, while calling for the identification of glial targets for the development of more specific antiepileptic drugs [18].…”

Section: Introductionmentioning

confidence: 99%

Expression of Cytoskeletal Proteins (GFAP, Vimentin), Proapoptotic Protein (Caspase-3) and Protective Protein (S100) in the Epileptic Focus in Adults and Children with Drug-Resistant Temporal Lobe Epilepsy Associated with Focal Cortical Dysplasia

Sitovskaya,

Zabrodskaya,

Parshakov

et al. 2023

IJMS

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The European Commission of the International League Against Epilepsy (ILAE) has identified glial mechanisms of seizures and epileptogenesis as top research priorities. The aim of our study was to conduct a comparative analysis of the expression levels of cytoskeletal proteins (glial fibrillar acidic protein (GFAP) and vimentin), protective protein S100, and proapoptotic caspase-3 protein in patients with drug-resistant epilepsy (DRE) associated with focal cortical dysplasia (FCD). We aimed to investigate how the expression levels of these proteins depend on age (both in children and adults), gender, and disease duration, using immunohistochemistry. Nonparametric statistical methods were employed for data analysis. In the epileptic focus area of the cortex and white matter in patients with FCD-associated temporal lobe DRE, a higher level of expression of these proteins was observed. Age and gender differences were found for vimentin and S100. In the early stages of disease development, there was a compensatory sequential increase in the expression of cytoskeletal and protective proteins. In patients with DRE, depending on the disease duration, patterns of development of neurodegeneration were noted, which is accompanied by apoptosis of gliocytes. These results provide insights into epilepsy mechanisms and may contribute to improving diagnostic and treatment approaches.

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Section: Introductionmentioning

confidence: 99%

Expression of Cytoskeletal Proteins (GFAP, Vimentin), Proapoptotic Protein (Caspase-3) and Protective Protein (S100) in the Epileptic Focus in Adults and Children with Drug-Resistant Temporal Lobe Epilepsy Associated with Focal Cortical Dysplasia

Sitovskaya,

Zabrodskaya,

Parshakov

et al. 2023

IJMS

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“…Astrocyte apoptosis is assumed to activate during and after a convulsive attack and may contribute to neuronal death and epileptogenesis [63]. Our studies have demonstrated that apoptosis can be observed mainly in oligodendrocytes, single astrocytes, and a small part of neurons only (Figure 8) [40,64,65].…”

Section: Glioneuronal Apoptosismentioning

confidence: 76%

Epileptic Focus in Drug-Resistant Epilepsy: Structure, Organization, and Pathophysiology

Zabrodskaya¹,

Gaykova²,

Alexandrov³

et al. 2023

Epilepsy - Seizures Without Triggers

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The chapter focuses on how different cutting-edge techniques can be used to study electrophysiological, pathomorphological, and biochemical changes in the “epileptic focus” area of the cerebral cortex and white matter to see how epileptic seizures become drug-resistant and how it affects the other regions of the brain. The authors highlight the significance of neuroinflammation and apoptosis in the epilepsy pathogenesis providing EEG characteristics and describing structural changes in the cortex and white matter under such conditions as focal cortical dysplasia and epileptic leukoencephalopathy. Particular focus is given to structural and functional changes in the hippocampus and the role of hippocampal sclerosis in epilepsy. Key conceptions regarding the epileptic focus formation are outlined.

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“…We have previously shown the presence of apoptosis and neuroinflammation in the temporal lobe of DRE patients [ 9 , 10 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis, oxidative stress, the loss of inhibitory or excitatory neurons, and inflammation play a key role in epilepsy progression [ 7 , 8 , 9 ]. We suggest that since the neuronal and glial components are closely related, it is necessary to study the functioning of both neurons and glia in epilepsy [ 10 ]. Reactive gliosis and inflammation accompanying neuronal damage contribute to the emergence of hyperexcitability focus [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Relationship between Neuroglial Apoptosis and Neuroinflammation in the Epileptic Focus of the Brain and in the Blood of Patients with Drug-Resistant Epilepsy

Соколова

Zabrodskaya

Литовченко

et al. 2022

IJMS

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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-α, p53 (Western blot), and cytokine levels in blood: IL-1β, IL-2, IL-4, IL-7, TNF-α, 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-α, FAS, NF-kB) were increased. The blood concentration of IL-4, IL-7, TNF-α 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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Apoptosis of Brain Cells in Epileptic Focus at Phapmacresistant Temporal Lobe Epilepsy

Cited by 7 publications

References 10 publications

Expression of Cytoskeletal Proteins (GFAP, Vimentin), Proapoptotic Protein (Caspase-3) and Protective Protein (S100) in the Epileptic Focus in Adults and Children with Drug-Resistant Temporal Lobe Epilepsy Associated with Focal Cortical Dysplasia

Expression of Cytoskeletal Proteins (GFAP, Vimentin), Proapoptotic Protein (Caspase-3) and Protective Protein (S100) in the Epileptic Focus in Adults and Children with Drug-Resistant Temporal Lobe Epilepsy Associated with Focal Cortical Dysplasia

Epileptic Focus in Drug-Resistant Epilepsy: Structure, Organization, and Pathophysiology

Relationship between Neuroglial Apoptosis and Neuroinflammation in the Epileptic Focus of the Brain and in the Blood of Patients with Drug-Resistant Epilepsy

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