Investigation of aquaporin-4's intermediation on antiepileptic efficacy of uridine in an animal model of epilepsy

The aim of this study is to investigate alterations in amount of brain edema, blood-brain barrier permeability, total aquaporin-4 and α1-syntrophin levels in the lithium-pilocarpine induced status epilepticus model and the possible role of uridine treatment on these parameters. In the study, 200-250 g, 6-8 weeks old, male 112 Sprague-Dawley rats were used. The study was designed as Sham, Control an Status epilepticus groups. Status epilepticus was induced by administration of lithium and pilocarpine. Control groups were treated identically but received 0.9% NaCl instead of pilocarpine. Sham groups were treated with 0.9% NaCl only. Rats were observed for 48 hours and received 0.9% NaCl or 500mg/kg uridine twice a day. Following 48 hours rats were sacrified and brain tissues and blood samples were collected. Brain water content was assesed by wet-dry weight method. S100B protein content was analyzed with ELISA in hippocampus homogenates and serum. Total aquaporin-4, α1-syntrophin and β-actin proteins were analyzed in hippocampus homogenates using Western-blot technique. Uridine treatment significantly increased brain edema. But it also prevented the decrease in total aquaporin-4 and α1-syntrophin levels and decreased serum S100B levels. S100B levels in hippocampus were higher in uridine-treated group. As a result, it is shown that uridine prevents loss of aquaporin-4 polarization and decreases blood-brain barrier permeability at 48 hours post status epilepticus which is suggested as it's neuroprotective efficacy. It is therefore likely that uridine treatment increased brain edema with an AQP4-independent pathway.