D. Sitovskaia, A. Litovchenko, E. Bazhanova, E. Skiteva, Yu. M. Zabrodskaia
{"title":"局灶性耐药癫痫患者外周血和脑细胞因子谱的变化","authors":"D. Sitovskaia, A. Litovchenko, E. Bazhanova, E. Skiteva, Yu. M. Zabrodskaia","doi":"10.47093/2218-7332.2021.12.4.39-50","DOIUrl":null,"url":null,"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.","PeriodicalId":129151,"journal":{"name":"Sechenov Medical Journal","volume":"509 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cytokine profile in the peripheral blood and the brain in patients with focal drug-resistant epilepsy\",\"authors\":\"D. Sitovskaia, A. Litovchenko, E. Bazhanova, E. Skiteva, Yu. M. Zabrodskaia\",\"doi\":\"10.47093/2218-7332.2021.12.4.39-50\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":129151,\"journal\":{\"name\":\"Sechenov Medical Journal\",\"volume\":\"509 1\",\"pages\":\"0\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-11-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Sechenov Medical Journal\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.47093/2218-7332.2021.12.4.39-50\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sechenov Medical Journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.47093/2218-7332.2021.12.4.39-50","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
的目标。探讨抗药癫痫(PhRE)患者血脑屏障功能障碍(BBB)的标志物——脑毛细血管内皮细胞中VEGF的含量、脑组织中TNF-α的含量及血清中细胞因子的含量。材料和方法。该研究包括30例接受颞叶前部切除术的PhRE患者。检测脑组织组织样本,评估VEGF和TNF-α的含量;测定血清中细胞因子的浓度。PhRE组致痫灶中表达VEGF的细胞密度及TNF-α含量均高于对照组(p < 0.001;P < 0.05)。与对照组比较,血清IL-2浓度(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)和EGF(43.72±5.63 pg/ml vs. 83.62±24.06 pg/ml;p < 0.05), TNF-α(33.09±1.23 pg/ml比24.85±1.32 pg/ml, p < 0.05)、IL-4(43.73±2.57 pg/ml比32.37±5.80 pg/ml, p < 0.05)、IL-5(43.73±2.57 pg/ml比32.37±5.80 pg/ml;p < 0.05), IL-7(16.65±3.07 pg/ml∶8.13±1.67 pg/ml;p < 0.05), GRO(生长调节蛋白)(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),差异有统计学意义。PhRE组与对照组IL-1β、IL-1RA、IL-10、IFN-γ的浓度差异无统计学意义。根据研究的细胞因子谱,PhRE患者没有全身性炎症。脑组织中VEGF的过度表达和血液中VEGF浓度的增加,加上血清EGF浓度的降低和GRO以及促炎因子的增加,表明血脑屏障受损。癫痫灶中高含量的TNF-α表明神经炎症,并且在血脑屏障功能障碍患者的血液中可以发现该标志物浓度升高。
Cytokine profile in the peripheral blood and the brain in patients with focal drug-resistant epilepsy
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.