Abstracts

There is increasing evidence that immune and inflammatory processes in early life are capable of producing lasting effects on physiology and CNS function and raise the possibility that a single inflammatory episode during development could evoke changes in seizure susceptibility later in adulthood., To explore this hypothesis, postnatal day 14 male rats received either the bacterial endotoxin lipopolysaccharide (LPS) (25-250 [micro]g/kg), or the viral mimetic Polyinosinic:Polycitydylic acid (POLY I:C) (1 mg/kg) to induce a mild inflammatory process. Two months later, rats received lithium and pilocarpine (LI-PILO), kainic acid (KA) or were subjected to amygdala kindling to discern any changes to seizure susceptibility. Following KA seizures, subsets of animals were killed and brains evaluated for neurodegeneration using Fluoro jade histochemistry., Neonatally LPS-treated, but not POLY I:C-treated rats, showed significantly faster seizure onset times (SOTs), by about 25% compared to controls. Adult rats given LPS and then LI-PILO two months later, did not show the same reduction in SOT as found with the neonatal treatment. Separate experiments determined a comparable susceptibility of neonatally LPS-treated rats to adult convulsions evoked with KA, but not to amygdala kindling. Behavioural sensitivities to KA were also reflected in the amount of neuronal degeneration in the CA3 and CA1 hippocampus 24 h after SOT., Taken together, we have observed that long-lasting changes in seizure susceptibility can be evoked following a mild inflammatory episode during development, possibly through a mechanism involving, or specific to, the Toll-like receptor (TLR)-4 (LPS-activated), but not TLR-3 (POLY I:C-activated) pathways., (Supported by Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Council of Canada (NSERC), and the Alberta Heritage Foundation for Medical Research (AHFMR).)