Anticonvulsive Effect of Folic Acid in Homocysteine Thiolactone-Induced Seizures

Abstract

Numerous studies have linked folate deficiency and resultant elevated plasma homocysteine levels with an increased risk of neurodegenerative diseases and seizures. The aim of the present study was to examine the effect of acute folic acid administration on behavioural and electroencephalographic (EEG) characteristics of DL homocysteine thiolactone-induced seizures in adult rats. Adult male Wistar rats were divided into following groups: (1) saline-treated (C); (2) DL homocysteine thiolactone 8 mmol/kg, i.p. (H); (3) groups that received folic acid i.p. in doses: 5 mg/kg (F(5)), 10 mg/kg (F(10)) and 15 mg/kg (F(15)) and (4) F 30 min prior to H (F(5)H, F(10)H and F(15)H, respectively). Seizure behaviour was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. For EEG recordings, under pentobarbital anaesthesia three gold-plated recording electrodes were implanted into the skull. There were no behavioural and EEG signs of seizure activity in C, F(5), F(10) and F(15) groups. In F(15)H group, the incidence of seizures was significantly lower, and the latency significantly prolonged, comparing to the H. Pre-treatment with F did not affect median number and severity of seizure episodes in all FH groups. Administration of F decreased mean total spectral power density in all FH groups, in a dose-dependent manner, in comparison with H. Our findings suggest that folic acid has anticonvulsive and antiepileptic effect on H-induced seizures in adult rats.