Postnatal systemic inflammation exacerbates impairment of hippocampal synaptic plasticity in an animal seizure model

To investigate the effects of systemic inflammation in the critical postnatal stages on neurophysiological actions of immune processes and neural plasticity in adult rats after kainic acid (KA)-induced seizures.

To determine changes in hippocampal synaptic plasticity after postnatal central nervous system inflammatory responses and seizure attacks, we performed intraperitoneal injections of lipopolysaccharide (LPS) in postnatal Sprague Dawley rats on day 14 (P14) to induce central nervous system inflammation. We then used a KA tail vein injection on P35 to induce seizure attacks. We compared the variability in synaptic plasticity in the hippocampal Schaffer collateral-CA1 region of seizure animals with or without LPS-induced inflammation preconditioning.

P14 injection of LPS increased susceptibility to seizures, while treatment with KA on P35 induced seizures. Long-term potentiation (LTP) of the Schaffer collateral-CA1 region was impaired in seizure animals, and this effect was more pronounced in the P14 LPS injection group. Fluoro-Jade staining revealed an increase in degenerated hippocampal CA1 pyramidal cells in the P14 LPS injection group. Cytokine expression in the hippocampus in the pre-, peri- and postictus periods was greater in P14 LPS rats than in saline-treated rats.

Intraperitoneal LPS injection on P14 induces higher cytokine secretion after KA-induced seizures, enhancing neuronal excitability, shortening seizure onset time and exacerbating neuronal degeneration and impairment of LTP formation in the hippocampal Schaffer collateral-CA1 region. Central nervous system inflammation during critical stages of childhood development could disrupt the balance needed for neurophysiological actions of immune processes, producing direct, pernicious effects on memory, neural plasticity and neurogenesis into adulthood.