In normal rats the proinflammatory cytokines like interleukin-1?, interleukin-6, which
are induced by bacterial lipopolysaccharides, are able to control thalamo-cortical
excitability by exerting strong effects on physiological synchronization such as sleep
and on pathological synchronization like that in epileptic discharges. To investigate
whether proinflammatory cytokines or lipopolysaccharides could modulate absence seizures
resulting from a very different generator mechanism than the already investigated
bicuculline-, kindling- and kainate-induced seizures, we used a genetically epileptic
Wistar Albino Glaxo/Rijswijk rat strain, which is spontaneously generating high voltage
spike-wave discharges. Wistar Albino Glaxo/Rijswijk rats responded with an increase
of the number of spike-wave discharges to lipopolysaccharide injection (from 10 ?g/kg
to 350 ?g/kg). Repetitive administration of 350 ?g/kg lipopolysaccharides daily for
5 days increased the number of spike-wave discharges on the first, second and third
days but the number of spike-wave discharges returned to the control value on day
5, at the 5th injection of lipopolysaccharides, showing a tolerance to lipopolysaccharides.
The lipopolysaccharide-induced increase in spike-wave discharges was not directly
correlated with the elevation of the core body temperature, as it is in febrile seizures,
although lipopolysaccharide induced prostaglandin and is clearly pyrogenic at the
doses used. Indomethacin, the prostaglandin synthesis inhibitor, efficiently blocked
lipopolysaccharide-induced enhancement of spike-wave discharge genesis suggesting
that the spike-wave discharge facilitating effect of lipopolysaccharides involves
induction of cyclooxygenase 2 and subsequent synthesis and actions of prostaglandin
E2. Low dose (40 mg/kg, i.p.) of competitive N-methyl-d-aspartate receptor antagonist
2-amino-5-phosphonopentanoic acid, and low dose of lipopolysaccharide (20 ?g/kg) showed
a synergistic interaction to increase the number of spike-wave discharges, whereas
at supramaximal doses of lipopolysaccharide and the N-methyl-d-aspartate antagonist
no synergy was present. The data reveal a functional connection between absence epileptic
activity and lipopolysaccharide induction of prostaglandin synthesis and prostaglandin
action and suggest some common cellular targets in epilepsy and lipopolysaccharide-induced
inflammation. Š 2006 IBRO.
