Cytokine profile in the peripheral blood and the brain in patients with focal drug-resistant epilepsy
https://doi.org/10.47093/2218-7332.2021.12.4.39-50
Abstract
Aim. To study markers of blood-brain barrier dysfunction (BBB) in patients with pharmacoresistant epilepsy (PhRE) – the amount of VEGF in endotheliocytes of brain capillaries, TNF-α in brain tissue and cytokine profile in blood serum.
Materials and methods. The study included 30 patients with PhRE who underwent anterior temporal bloc resection. Histological samples of the brain were examined to assess the amount of VEGF and TNF-α; the concentration of cytokines in the blood serum was determined.
Results. In the PhRE group, the densitometric density of cells expressing VEGF and the amount of TNF-α in the epileptogenic focus were higher than in the control groups (p < 0.001; p < 0.05). Compared with the control, the serum concentrations of IL-2 (0.98 ± 0.28 pg/ml vs. 2.80 ± 0.71 pg/ml; p < 0.001), IL-8 (14.04 ± 1.46 pg/ml vs. 26.13 ± 3.80 pg/ml; p < 0.001) and EGF (43.72 ± 5.63 pg/ml vs. 83.62 ± 24.06 pg/ml; p < 0.05) were statistically significantly lower in the PhRE group, and the amount of TNF-α (33.09 ± 1.23 pg/ml vs. 24.85 ± 1.32 pg/ml, p < 0.05), IL-4 (43.73 ± 2.57 pg/ml vs. 32.37 ± 5.80 pg/ml, p < 0.05), IL-5 (43.73 ± 2.57 pg/ml vs. 32.37 ± 5.80 pg/ml; p < 0.05), IL-7 (16.65 ± 3.07 pg/ml vs. 8.13 ± 1.67 pg/ml; p < 0.05), GRO (growth-regulated protein) (3054.0 ± 200.8 pg/ml vs. 1367.0 ± 187.3 pg/ml; p < 0.001), VEGF (316.10 ± 55.28 pg/ml vs. 95.22 ± 15.78 pg/ml; p < 0.01) are statistically significantly higher. There were no significant differences in the concentration of IL-1β, IL-1RA, IL-10 and IFN-γ between the PhRE group and the control.
Conclusion. Based on the studied cytokine profile, there is no systemic inflammation in patients with PhRE. The established overexpression of VEGF in the brain and an increase in its concentration in the blood, combined with a decrease in serum EGF concentrations and an increase in GRO, as well as pro-inflammatory factors, indicates damage to the BBB. A high amount of TNF-α in the epileptic focus indicates neuroinflammation, and an increased concentration of this marker can be found in the blood of patients with BBB dysfunction.
About the Authors
D. A. Sitovskaia
Polenov Neurosurgical Institute – Branch of Almazov National Medical Research Centre;
Saint Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
pathologist, researcher, Research Laboratory of Nervous System Pathomorphology; Assistant Professor, Department of Pathology
Tel.: +7 (981) 761-31-97
12, Mayakovskogo str., Saint-Petersburg, 191014, Russia
2, Litovskaya str., Saint-Petersburg, 194100, Russia
A. V. Litovchenko
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Russian Federation
Russian Federation
post-graduate student, Laboratory of Comparative Biochemistry and Cellular Functions
44, Toreza av., Saint-Petersburg, 194223, Russia
E. D. Bazhanova
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences;
Golikov Research Clinical Center of Toxicology under the Federal
Medical Biological Agency;
Astrakhan State University
Russian Federation
Russian Federation
Dr. of Sci. (Med.), Leading Researcher, Laboratory of Comparative Biochemistry and Cellular Functions; Head of the Laboratory of Morphology and Electron Microscopy; Senior Researcher, Department of Biochemistry
44, Toreza av., Saint-Petersburg, 194223, Russia
1, Bechtereva str., Saint-Petersburg, 192019, Russia
20a, Tatischeva str., Astrakhan, 414000, Russia
E. N. Skiteva
Polenov Neurosurgical Institute – Branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
junior researcher, Research Laboratory of Nervous System Pathomorphology
12, Mayakovskogo str., Saint-Petersburg, 191014, Russia
Yu. M. Zabrodskaia
Polenov Neurosurgical Institute – Branch of Almazov National Medical Research Centre;
Golikov Research Clinical Center of Toxicology under the Federal Medical Biological Agency;
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
Dr. of Sci. (Med.), Head of the Research Laboratory of Nervous System Pathomorphology; Leading Researcher, Laboratory of Morphology and Electron Microscopy; Associate Professor, Department of Pathology
12, Mayakovskogo str., Saint-Petersburg, 191014, Russia
1, Bechtereva str., Saint-Petersburg, 192019, Russia
6, Academician Lebedev str., Saint-Petersburg, 194044, Russia
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Supporting agencies: The study of citokines was carried out within the framework of the RFBR grant № 20-015-00127 and on the equipment of the CCU of the IEFB RAS. Immunohistochemical study was performed within the framework State task No. 121031000359-3 "Development of new approaches in the diagnosis of mediobasal pharmacoresistant epilepsy based on histoproteomics of epileptic foci".
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