The effects of TGN-020 on penicillin induced epileptiform activity in rats

Abstract

Objective: Aquaporin-4 (AQP-4) is a water channel protein which is the most abundant aquaporin isoform in the brain. Recent studies indicate the relationship between AQP-4 with epileptogenesis. Therefore, we examined the potential effect of the AQP-4 inhibitor TGN-020 on penicillin-induced epileptiform activity in rats.

Material and Method: Epileptiform activity was induced by intracortical (i.c.) administration of penicillin (200 IU, 1 μl). TGN-020, at doses of 25 µg, 50 µg, 100 µg and 200 µg, was administered by intracerebroventricular (i.c.v.) 30 minutes after penicillin injection. The epileptiform activity was verified by electrocorticographic (ECoG) recordings. Twenty four hours later, animals are decapitated for the collection of blood samples and brain tissue.

Results: The dose of 100 µg TGN-020 decreased the mean spike frequency of epileptiform activity in the 30 min after the injection without changing the amplitude (p < 0.05). Serum neuropeptide Y level was up-regulated by 25 µg TGN-020 in comparison with the other groups (p<0.001). Plasma levels of calcineurin in the 50 µg dose of TGN-020 were lower than 25 µg and 200 µg doses of TGN-020 (p<0.01). Enzymatic ativity of glutathione peroxidase (GP_x-1) in brain tissue was higher in the penicillin and 25 µg TGN-020 group compared with the sham group (p < 0.05).

Conclusion: Given all these data, the anticonvulsant effect of TGN-020 which is aquaporin-4 water channel inhibitor in the brain has been studied extensively for the first time in an experimental model of epilepsy. Inhibition of AQP-4 might be useful in the treatment of epilepsy in future.

Keywords

• TGN-020,Aquaporin 4,Epilepsy,EcoG,DMSO,Neuropeptide Y

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