EEG spectra and glial transformations following seizures induced in rats pretreated with systemic inflammation at two developmental stages

We examined the extent to which reactive glial transformations correspond to the degree of seizure reactivity in adult rats after experiencing inflammation at different developmental stages. In 6- or 30-day-old rats, systemic inflammation was induced with lipopolysaccharide (LPS). At the age of two months, the LPS-treated rats and controls were implanted with EEG teletransmitters and seizures were induced with pilocarpine. Before and during the seizures, EEG recordings were performed and changes in EEG spectra and intensity of behavioral seizure symptoms were analyzed. Brain sections were immunostained for GFAP and Iba1 to visualize astrocytes and microglia, respectively, and ramification degrees of their processes were assessed. No significant effects of the generalized inflammation alone evoked at any developmental stage were observed in EEG recordings in adulthood. Then, seizures were induced with pilocarpine and significant changes appeared in EEG spectra depending on the age of LPS application. In the same respect, significant correlations were detected between the degrees of ramification of astroglial or microglial processes and the power of EEG signal and/or its particular frequency bands. Thus, the initial effects of inflammation remained undetected up till adulthood and became revealed with a “second hit”procedure using pilocarpine as a seizuregenic factor. As revealed by correlation analyses, the effects were strongly reflected by the degree of astrocyte transformations and considerably weaker by microglia. These results indicate a strong, possibly causal involvement of glial reactivity in long-term functional changes in the brain following general inflammation at different developmental stages.