Long-term monotherapy treatment with vitamin E reduces oxidative stress, but not seizure frequency in rats submitted to the pilocarpine model of epilepsy.

The imbalance between antioxidant system and reactive oxygen species (ROS) generation is related to epileptogenesis, neuronal death, and seizure frequency. Treatment with vitamin E has been associated with neuroprotection and control of seizures. In most experimental studies, vitamin E treatment has short duration. Therefore, the aim of this study was to verify the role of long-term treatment with vitamin E in rats submitted to the pilocarpine model of epilepsy. Rats were divided into two main groups: control (Ctr) and pilocarpine (Pilo). Each one was subdivided according to treatment: vehicle (Ctr V and Pilo V) or vitamin E at dosages of 6 IU/kg/day (Ctr E6 and Pilo E6) or 60 IU/kg/day (Ctr E60 and Pilo E60). Treatment lasted 120 days from status epilepticus (SE). There were no statistical differences concerning treatment in the Ctr group for all variables, so the data were grouped. Carbonyl content in the hippocampus of Pilo V and Pilo E6 was higher compared with that of the Ctr group (8 ±â€¯1.5, 7.1 ±â€¯1, and 3.1 ±â€¯0.3 nmol carbonyl/mg protein, respectively for Pilo V, Pilo E6, and Ctr; p < 0.05). Carbonyl content was restored to control values in Pilo E60 rats (4.2 ±â€¯1.1 and 3.1 ±â€¯0.3 nmol carbonyl/mg protein, respectively for Pilo E60 and Ctr; p > 0.05). The volume of the hippocampal formation (6.5 ±â€¯0.3, 6.6 ±â€¯0.4, 6.3 ±â€¯0.3, and 7.4 ±â€¯0.2, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and subfields CA1 (1.6 ±â€¯0.1, 1.4 ±â€¯0.2, 1.5 ±â€¯0.1, and 2 ±â€¯0.05, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and CA3 (1.7 ±â€¯0.1, 1.5 ±â€¯0.2, 1.4 ±â€¯0.1, and 2 ±â€¯0.1, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) was reduced in the Pilo group regardless of treatment. Parvalbumin immunostaining was increased in the hilus of the Pilo E60 group compared with that in the Ctr group (26 ±â€¯2 and 39.6 ±â€¯8.3 neurons, respectively for Ctr and Pilo E60). No difference was found in seizure frequency and Neo-Timm staining. Therefore, long-term treatment with 60 IU/kg/day of vitamin E prevented oxidative damage in the hippocampus and increased hilar parvalbumin expression in rats with epilepsy without a reduction in seizure frequency.

Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids.

Studies have provided evidence of the important effects of omega-3 fatty acid on the brain in neurological conditions, including epilepsy. Previous data have indicated that omega-3 fatty acids lead to prevention of status epilepticus-associated neuropathological changes in the hippocampal formation of rats with epilepsy. Omega-3 fatty acid supplementation has resulted in extensive preservation of GABAergic cells in animals with epilepsy. This study investigated the interplay of these effects with neurogenesis and brain-derived neurotrophic factor (BDNF). The results clearly showed a positive effect of long-term omega-3 fatty acid supplementation on brain plasticity in animals with epilepsy. Enhanced hippocampal neurogenesis and BDNF levels and preservation of interneurons expressing parvalbumin were observed. Parvalbumin-positive cells were identified as surviving instead of newly formed cells. Additional investigations are needed to determine the electrophysiological properties of the newly formed cells and to clarify whether the effects of omega-3 fatty acids on brain plasticity are accompanied by functional gain in animals with epilepsy.

Neuroprotective activity of omega-3 fatty acids against epilepsy-induced hippocampal damage: Quantification with immunohistochemical for calcium-binding proteins.

To investigate whether n-3 polyunsaturated fatty acids (n-3 PUFAs) would promote different morphological changes in the hippocampal formation of rats with epilepsy, we performed an immunocytochemical study using parvalbumin (PV) and calretinin (CR) distribution as a marker. Animals subjected to the experimental model of epilepsy with a single dose of pilocarpine were randomly divided into the following groups: animals with epilepsy treated daily with vehicle (EV) and animals with epilepsy treated daily with 85 mg/kg n-3 PUFAs (EW). Control animals administered saline were also randomly divided into two other groups: animals treated daily with vehicle (CV) and animals treated daily with 85 mg/kg n-3 PUFAs (CW). A larger number of PV-positive neurons were observed in EW when compared with EV, CV, and CW. Similarly, there were significantly more CR-positive neurons in EW than in EV. These findings demonstrate that omega-3 fatty acids prevent status epilepticus-associated neuropathological changes in the hippocampal formation of rats with epilepsy.