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

Year 2018, , 303 - 311, 30.08.2018

Enes Akyuz , Mukaddes Pala Ramazan Kozan , Hayrullah Kose

https://doi.org/10.17546/msd.451398

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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