Abstracts

Rationale: Systemic inflammation leads to a number of the mediated physiological changes in central nervous system. The underlying mechanisms and the signaling pathways involved in these phenomena remain yet well understood. We hypothesized that peripheral inflammation leads to increased neuronal excitability arising from a CNS immune response. The research aim was to investigate the role of activated microglia in seizure susceptibility of the mice following sepsis. Methods: We induced inflammation by administration (i.p.) of lipopolysaccharide (LPS) to adult male mice. Seven days later, the LPS-treated mice were randomly assigned to treat daily with vehicle, dextromethorphan 15 mg/kg, apocynin 10 mg/kg. To examine the excitability of the brain in vivo, we administered pentylenetetrazole (i.p.) to evoke clonic seizures. In vitro hippocampal slices from the mice were performed to measure spontaneous interictal burst firing. Results: The LPS-treated mice exhibited a marked, persistent inflammatory response within the hippocampus, characterized by microglial activation. Mice treated with apocynin showed decreased susceptibility to PTZ seizures compared with those with vehicle treatment. In vitro hippocampal slices from LPS-treated mice showed increased spontaneous interictal burst firing, which was attenuated in the apocynin-treated mice. Conclusions: Peripheral inflammation induced persistent neuro-inflammation and, such as microglia activation, and increased seizure susceptibility in mice. By inhibition of microglia activation, apocynin demonstrated to attenuate intrinsic excitability in hippocampus and recovery seizure threshold in LPS-treated mice. Our finding of a microglia-mediated increase in CNS excitability provides insight into potential mechanisms underlying the disparate neurological change following systemic inflammation.