Modulation of Epileptic Activity in Rats: Focus on Sleep, Physical Exercise and Nitric Oxide–mediated Neurotransmission in a Model of Homocysteine Thiolactone–induced Seizures

Epilepsija je hronično neurološko oboljenje koje karakteriše rekurentna pojava epileptičnih napada. Razumevanje menahizama nastanka i širenja epileptične aktivnosti, kao i foktora modulacije ovih procesa, od izuzetnog je naučnostručnog značaja. Eksperimentalni modeli epilepsije su značajni za razumevanje upravo ovih mehanizama

Different Sensitivity of Various Brain Structures to Thioacetamide-Induced Lipid Peroxidation

Thioacetamide (TAA) exerts hepatotoxic, neurotoxic and carcinogenic effects. The aim of our study was to investigate the effects of TAA on lipid peroxidation and catalase activity in various rat brain regions. Male Wistar rats were divided into following groups: 1. control, saline-treated; 2. thioacetamide-treated groups, TAA(300) (300 mg/kg), TAA(600) (600 mg/kg) and TAA(900) (900 mg/kg). Daily dose of TAA (300 mg/kg) was administered intraperitoneally once (TAA(300)), twice (TAA(600)) and three times (TAA(900)) in consecutive days. Brain samples were collected 24 h after the last dose of TAA and malondialdehyde (MDA) level and catalase activity were determined in cortex, brainstem and hippocampus. MDA level was significantly increased while catalase activity was significantly lower in all brain regions in TAA(900) group in comparison with control group. In TAA(600) MDA level was increased in the brainstem and cortex when compared to control (p LT 0.01). The same dose of TAA(600) mg/kg induced a significant decline in catalase activity in the brainstem and cortex and an increase in its activity in the hippocampus when compared to control (p LT 0.01). In TAA(300) an increase in MDA level was evident only in the brainstem. Catalase activity was significantly higher in the cortex and hippocampus in TAA(300) group in comparison with control (p LT 0.01). Based on these results, it may be concluded that various rat brain regions have different sensitivity to TAA-induced lipid peroxidation with hippocampus being less sensitive than cerebral cortex and brainstem

The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration

Hyperhomocysteinemia is associated with various pathologies including cardiovascular disease, stroke, and cognitive dysfunctions. Systemic administration of homocysteine can trigger seizures in animals, and patients with homocystinuria suffer from epileptic seizures. Available data suggest that homocysteine can be harmful to human cells because of its metabolic conversion to homocysteine thiolactone, a reactive thioester. A number of reports have demonstrated a reduction of Na+/K+-ATPase activity in cerebral ischemia, epilepsy and neurodegeneration possibly associated with excitotoxic mechanisms. The aim of this study was to examine the in vivo effects of d,l-homocysteine and d,l-homocysteine thiolactone on Na+/K+- and Mg2+-ATPase activities in erythrocyte (RBC), brain cortex, hippocampus, and brain stem of adult male rats. Our results demonstrate a moderate inhibition of rat hippocampal Na+/K+-ATPase activity by d,l-homocysteine, which however expressed no effect on the activity of this enzyme in the cortex and brain stem. In contrast,d,l-homocysteine thiolactone strongly inhibited Na+/K+-ATPase activity in cortex, hippocampus and brain stem of rats. RBC Na+/K+-ATPase and Mg2+-ATPase activities were not affected by d,l-homocysteine, while d,l-homocysteine thiolactone inhibited only Na+/K+-ATPase activity. This study results show that homocysteine thiolactone significantly inhibits Na+/K+-ATPase activity in the cortex, hippocampus, and brain stem, which may contribute at least in part to the understanding of excitotoxic and convulsive properties of this substance

Hyperhomocysteinemia Induced By Methionine Nutritional Overload More Promptly Affects Brain Than Heart Cholinergic System Without Affects on Food Intake and Body Mass Gain

85th Congress of the European-Atherosclerosis-Society (EAS), Apr 23-26, 2017, Prague, Czech Republi