What is it about?

We showed previously that the number and time of spike-wave discharges (SWDs) were increased after intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), an effect, which was completely abolished by cyclooxygenase-2 (COX-2) inhibitor indomethacin (IND) pretreatment in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. These and other results suggest that injection of LPS to genetically absence epileptic animals, such as WAG/Rij rats, may allow us to investigate relationships between absence epilepsy and LPS evoked neuroinflammation processes. However, LPS may evoke different effects on absence epileptic activity in various animal strains. Thus, to extend our previous results, we injected two doses of LPS (50 μg/kg and 350 μg/kg i.p.) alone and in combination with IND (10 mg/kg IND i.p. + 50 μg/kg LPS) into rats of two model animal strains (WAG/Rij rats; GAERS rats: Genetic Absence Epileptic Rats from Strasbourg) and into Long Evans rats. The effects of treatments on SWD number and SWD duration were examined. Both doses of LPS increased the SWD number and the total time of SWDs dose-dependently during the whole 4-hour recording period, which was abolished by IND pretreatment in all three investigated strains.

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Why is it important?

These results extend our previous results suggesting that our methods using LPS injection into freely moving absence epileptic rats is applicable not only in well-established animal models of absence epilepsy such as WAG/Rij rats and GAERS rats but also in Long Evans rats to investigate links between inflammation and absence epilepsy.

Perspectives

The results of this study also suggest that Long Evans rat strain could be an animal model of human absence epilepsy as the experimental results obtained in these rats are similar to the experimental results obtained in the well-known animal models (WAG/Rij and GAERS) of human absence epilepsy. These results extend our previous data suggesting that our methods based on LPS injection into freely moving absence epileptic rats are broadly applicable across rat models of absence epilepsy (such as WAG/Rij rats and GAERS rats) and Long Evans rats, to investigate the links between the activation of the inflammatory/cytokine system, the excitability of neuronal networks and the absence epileptic activity as well as the beneficial and adverse effects of new anti-inflammatory/anti-epileptic drugs, such as TLR4 antagonists.

Dr Zsolt Kovacs
Eötvös Loránd University

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This page is a summary of: Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and Long Evans rats, Brain Research Bulletin, May 2014, Elsevier,
DOI: 10.1016/j.brainresbull.2014.03.003.
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