Neuroinflammation in the pathogenesis of the audiogenic epilepsy: altered proinflammatory cytokine levels in Krushinsky-Molodkina seizure-prone rats

Abstract

Neuroinflammation plays an important role in epileptogenesis, however, most studies are performed on pharmacological models of epilepsy, while data on non-invasive, including genetic, models are practically absent. In Krushinsky-Molodkina (KM) strain rats with high genetically caused predisposition to AE (intensive audiogenic seizure fit in response to the action of sound) and in the control strain “0” (not predisposed to AE), the levels of a number of pro-inflammatory cytokines were investigated 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 KM rats were significantly lower than in rats “0” (32.31, 27.84 and 38.87% of decrease, respectively, p < 0.05, 0.05 and 0.01), whereas in the brain stem in the “background” state of interstrain differences in levels of these metabolites were not detected. 4 h after sound exposure, the TNF-α level in the dorsal striatum of KM rats was significantly (38.34%, p < 0.01) lower than in “0” rats. In KM rats, after the action of sound and the subsequent seizure fit, the levels of IL-1β and IL-6 in the dorsal striatum were significantly higher compared to the background (35.29 and 50.21%, of increase, p < 0.05, 0.01, respectively). The IL-2 level in KM rats in the background state was not detected, whereas after audiogenic seizures its level was 14.01 pg/ml (significantly higher, p < 0.01). In the brain stem of KM rats, the levels of IL-1β and TNF-α after audiogenic seizures were significantly lower than in the background (13.23 and 23.44% of decrease, respectively, p < 0.05). In rats of the “0” strain, the levels of cytokines in the dorsal striatum after the action of sound (which did not cause AE seizures) did not differ from those in the background, while the levels of IL-1β in their brain stem 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 rats that differed in their predisposition to AE, which suggests the involvement of these metabolites in the pathophysiology of epilepsy.