Intracerebroventricularly administered lipopolysaccharide enhances spike–wave discharges

What is it about?

Peripheral lipopolysaccharide (LPS) injection enhances spike-wave discharges (SWDs) in the genetic rat model of absence epilepsy (Wistar Albino Glaxo/Rijswijk rats: WAG/Rij) but the effect of centrally administered LPS is unknown. To examine this question we intracerebroventricularly (i.c.v.) injected LPS into WAG/Rij rats and measured the number and duration of SWDs. As a combined treatment, a non-steroid anti-inflammatory drug (indomethacine: IND) and a competitive N-methyl-D-aspartate (NMDA) receptor antagonist (2-Amino-5-phosphonopentanoic acid: AP5) was injected intraperitoneally (i.p.) parallel with the i.c.v. LPS application. I.c.v. injected LPS increased the number and duration of SWDs for 3 hours but later a decrease in epileptic activity was observed. IND abolished the i.c.v. LPS induced changes in SWDs. The AP5 application alone decreased the number of SWDs, but surprisingly the combined application of AP5 with i.c.v. LPS increased the SWD number for 5 hours.

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Why is it important?

Our results show, that the centrally injected LPS increases the number and duration of SWDs in the WAG/Rij rats similarly to the peripheral injection but with a swifter dynamic. This effect was abolished by IND and extended by AP5 suggesting a role of centrally secreted proinflammatory cytokines in the modulation of absence epileptic-like activity.

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