Faculty of Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
Pirogov Russian National Research Medical University, Moscow, 117997, Russia.
Biochemistry (Mosc). 2023 Apr;88(4):481-490. doi: 10.1134/S0006297923040041.
Neuroinflammation plays an important role in epileptogenesis, however, most studies are performed using pharmacological models of epilepsy, while there are only few data available for non-invasive, including genetic, models. The levels of a number of pro-inflammatory cytokines were examined in the Krushinsky-Molodkina (KM) rat strain with high audiogenic epilepsy (AE) proneness (intense tonic seizure fit in response to loud sound) and in the control strain "0" (not predisposed to AE) using multiplex immunofluorescence magnetic assay (MILLIPLEX map Kit). Cytokine levels were determined in the dorsal striatum tissue and in the brain stem. Background levels of IL-1β, IL-6, and TNF-α in the dorsal striatum of the KM rats were significantly lower than in the rats "0" (by 32.31, 27.84, and 38.87%, respectively, p < 0.05, 0.05, and 0.01), whereas no inter-strain differences in the levels of these metabolites were detected in the brain stem in the "background" state. Four hours after sound exposure, the TNF-α level in the dorsal striatum of the KM rats was significantly lower (by 38.34%, p < 0.01) than in the "0" rats. In the KM rats, the dorsal striatal levels of IL-1β and IL-6 were significantly higher after the sound exposure and subsequent seizure fit, compared to the background (35.29 and 50.21% increase, p < 0.05, 0.01, respectively). In the background state the IL-2 level in the KM rats was not detected, whereas after audiogenic seizures its level was 14.01 pg/ml (significant difference, p < 0.01). In the KM rats the brain stem levels of IL-1β and TNF-α after audiogenic seizures were significantly lower than in the background (13.23 and 23.44% decrease, respectively, p < 0.05). In the rats of the "0" strain, the levels of cytokines in the dorsal striatum after the action of sound (which did not induce AE seizures) were not different from those of the background, while in the brain stem of the "0" strain the levels of IL-1β were lower than in the background (40.28%, p < 0.01). Thus, the differences between the background levels of cytokines and those after the action of sound were different in the rats with different proneness to AE. These data suggest involvement of the analyzed cytokines in pathophysiology of the seizure state, namely in AE seizures.
神经炎症在癫痫发生中起着重要作用，然而，大多数研究都是使用癫痫的药理学模型进行的，而对于非侵入性的，包括遗传的，模型，只有很少的数据可用。使用多重免疫荧光磁检测法（MILLIPLEX map Kit）检查了具有高听觉性癫痫（AE）易感性（对大声响反应强烈的强直性发作）的 Krushinsky-Molodkina（KM）大鼠品系和对照品系“0”（不易发生 AE）中许多促炎细胞因子的水平。细胞因子水平在背纹状体组织和脑干中测定。KM 大鼠背纹状体中 IL-1β、IL-6 和 TNF-α 的背景水平明显低于“0”大鼠（分别降低 32.31%、27.84%和 38.87%，p<0.05、0.05 和 0.01），而在“背景”状态下，这两种代谢物在脑干中的品系间差异不明显。在声音暴露后 4 小时，KM 大鼠背纹状体中的 TNF-α 水平明显低于“0”大鼠（降低 38.34%，p<0.01）。在 KM 大鼠中，与背景相比，声音暴露和随后的癫痫发作后，背纹状体中的 IL-1β 和 IL-6 水平显著升高（分别增加 35.29%和 50.21%，p<0.05、0.01）。在背景状态下，KM 大鼠中未检测到 IL-2 水平，而在听觉性癫痫发作后其水平为 14.01 pg/ml（差异显著，p<0.01）。在 KM 大鼠中，听觉性癫痫发作后，脑干中的 IL-1β 和 TNF-α 水平明显低于背景水平（分别降低 13.23%和 23.44%，p<0.05）。在“0”品系大鼠中，声音作用（未诱导 AE 发作）后背纹状体中细胞因子的水平与背景无差异，而在“0”品系大鼠的脑干中，IL-1β 的水平低于背景（降低 40.28%，p<0.01）。因此，具有不同 AE 易感性的大鼠中，细胞因子的背景水平与声音作用后的水平之间的差异不同。这些数据表明，所分析的细胞因子参与了癫痫状态的病理生理学，即 AE 癫痫发作。
