Inflammation in the developing rat modulates astroglial reactivity to seizures in the mature brain.

Astrocytes participate in neuronal development and excitability, and produce factors enhancing or suppressing inflammatory processes occurring due to neurodegenerative diseases, such as epilepsy. Seizures, in turn, trigger the release of inflammatory mediators, causing structural and functional changes in the brain. Therefore, it appears reasonable to determine whether generalized inflammation at developmental periods can affect astrocyte reactivity to epileptic seizures occurring in the adult brain. Lipopolysaccharide (LPS) was injected in 6- or 30-day-old rats (P6 or P30, respectively). At the age of 2 months, seizures were induced, and pilocarpine and morphological changes of astrocytes located within the hippocampal formation were assessed. Additionally, expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), aquaporin 4 (AQP4), and inwardly rectifying potassium channel Kir 4.1 (Kir4.1) was determined using Western blots. The animal group given LPS on P6 displayed maximal susceptibility to pilocarpine-induced seizures, significantly higher than the group that received LPS on P30. In the immunohistologically examined hippocampal formation, the GFAP-immunoreactive area was not affected by LPS alone. However, it was reduced following seizures in naïve controls but not in LPS-pretreated rats. Increases in the ramification of astrocytic processes were detected only in adult rats given LPS on P30, not on P6. Seizures abolished the effects. Following seizures, the process ramification showed no significant change in the two LPS-treated rat groups, whereas it was significantly reduced in the dentate gyrus of LPS-untreated controls. Glial fibrillary acidic protein (GFAP) expression showed no changes induced with LPS alone and rose slightly after seizures. AQP4 content was lower in rats given LPS on P6 and was seizure-resistant in the two LPS-treated groups, contrary to a decrease in untreated controls. GS expression was not affected by LPS treatments and was reduced after seizures without an intergroup difference. Kir4.1 underwent highly significant increases in all groups experiencing seizures, but LPS alone had no effect. It can be concluded that the generalized inflammatory status led to some important changes in astrocytes reflected, in part at least by permanent modifications of their morphology and molecular profile. Moreover, the previously experienced inflammation prevented the cells from much stronger changes in response to seizures observed in adult untreated controls. The obtained results point to a link between the activation of astrocytes by transient systemic inflammation occurring during the developmental period and their subsequent reactivity to seizures, which may play an important role in the functional features of the brain, including its susceptibility to seizures.