Abstracts

Uridine, a pyrimidine nucleoside essential for the synthesis of RNA and bio-membranes, is a crucial element in the regulation of normal physiological processes as well as pathological states. There is evidence that Uridine may improve the function of disturbed mitochondrial oxidative phosphorylation and ATP production through increasing cellular oxygen supply and using pyruvate, a fuel for ATP synthesis, more efficiently. We hypothesized that the molecule may be useful in altering epileptogenesis or in treating seizures. Male adult Sprague Dawley (n=36) rats were used. Under sterile conditions, Stimulating electrode was implanted in left ventral hippocampal commissure and recording electrode was put in CA1. We intravenously administered Uridine (100 mg/kg; n=12) or normal saline (n=24) three times a day. Rats were kindled with 2 sec, 20 Hz suprathreshold stimulus train 12 times a day till they had two consecutive stage 5 seizures. Following completion of the kindling, saline-treated rats underwent alternative administration of Uridine or normal saline and a single stimulation for 8 days. Uridine or normal saline were applied 15 minutes before the kindling stimulations. Rate of kindling and afterdischarge duration for each stimulation were compared in the uridine and saline treated groups. Uridine was well tolerated by the rats with none of the animals demonstrating any signs of toxicity. Uridine-treated rats had a slower rate of kindling than controls (ANOVA, repeated masures p=0.011) with the mean number of stimulations require to reach stage 5 kindling in the control rats (23.63[plusmn]2.89) lower than in the uridine-treated rats (32.50[plusmn]2.61)(p=0.038). In addition, in fully kindled rats the seizure score after uridine (3.6[plusmn]0.22) was lower than the NS group (4.1[plusmn]0.30)(p=0.007). There was also a non-significant decrease in afterdischarge duration in the uridine-treated (72.72[plusmn]8.16) compared to the NS-treated group (57.99[plusmn]4.33)(p=0.066). Our study shows that uridine has a modest anti-epileptogenesis and anticonvulsant effect. The compound may have potential as an add-on compound in the prevention or treatment of epilepsy. (Supported by RepliGen Corporation.)