O. Stanojlović

The effect of N-methyl-D-aspartate receptor antagonists on D,L-homocysteine thiolactone induced seizures in adult rats.

The aim of our study was to investigate the effects of ifenprodil and MK-801 on D,L-homocysteine thiolactone induced seizures in adult rats.Male Wistar rats were divided into following groups: 1. Saline-treated (C, n=10); 2. D,L-homocysteine thiolactone 8 mmol/kg, i.p. (H, n=7); 3. Ifenprodil 20 mg/kg i.p. (IF, n=8); 4. MK-801 0.5 mg/kg, i.p. (MK, n=8) and 5. Groups that received IF or MK 30 minutes prior to H (IFH, n=8 and MKH, n=8). Seizure behavior was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. Lethality in experimental group was recorded 90 min and 24 h upon D,L-homocysteine thiolactone administration.There were no behavioral signs of seizure activity in groups C, IF and MK.Pre-treatment with MK-801 (MKH) showed tendency to reduced incidence of convulsions, latency to the first seizure onset and the severity of seizure episodes, but statistical significance was not attained comparing to the H group. However, median number of seizure episodes was significantly decreased in MKH (p<0.05), comparing to the H group. On the other hand, ifenprodil (IFH) decreased the latency to the first seizure onset and increased the median number of seizure episodes (p<0.05). The majority of seizure episodes in IFH (72.1%, p<0.05) and MKH (73.1%, p<0.05) groups was grade 2 and significantly different comparing to the H (36.0%). Our findings suggest that MK-801 has a mild anticonvulsive effect on D,L-homocysteine thiolactone induced seizures in adult rats.

Homocysteine thiolactone-induced seizures in adult rats are aggravated by inhibition of inducible nitric oxide synthase

Homocysteine and its metabolites (homocysteine thiolactone (HT)) induce seizures via different but still not well-known mechanisms. The role of nitric oxide (NO) in epileptogenesis is highly contradictory and depends on, among other factors, the source of NO production. The aim of the present study was to examine the effects of aminoguanidine, selective inhibitor of inducible NO synthase (iNOS), on HT-induced seizures. Aminoguanidine (50, 75, and 100 mg/kg, intraperitoneally (i.p.)) was injected to rats 30 min prior to inducing HT (5.5 mmol/kg, i.p.). Seizure behavior was assessed by seizure incidence, latency time to first seizure onset, number of seizure episodes, and their severity during observational period of 90 min. Number and duration of spike and wave discharges (SWDs) were determined in electroencephalogram (EEG). Seizure latency time was significantly shortened, while seizure incidence, number, and duration of HT-induced SWD in EEG significantly increased in rats receiving aminoguanidine 100 mg/kg before subconvulsive dose of HT. Aminoguanidine in a dose-dependent manner also significantly increased the number of seizure episodes induced by HT and their severity. It could be concluded that iNOS inhibitor (aminoguanidine) markedly aggravates behavioral and EEG manifestations of HT-induced seizures in rats, showing functional involvement of iNOS in homocysteine convulsive mechanisms.

The effect of subchronic supplementation with folic acid on homocysteine induced seizures

Influence of folic acid on the CNS is still unclear. Folate has a neuroprotective effect, while on the other hand excess folate can exacerbate seizures in epileptics. The aim of the present study was to examine the effect of subchronic administration of folic acid on behavioural and electroencephalographic (EEG) characteristics of DL homocysteine thiolactone induced seizures in adult rats. The activity of Na⁺/K⁺-ATPase and Mg²⁺-ATPase in different brain regions was investigated. Adult male Wistar rats were divided into groups: 1. Controls (C, 0.9% NaCl); 2. DL homocysteine-thiolactone 8.0 mmol/kg (H); 3. Subchronic supplementation with folic acid 5 mg/kg for 7 days (F) and 4. Subchronic supplementation with F + single dose of H (FH). 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, three gold-plated recording electrodes were implanted into the skull. Subchronic supplementation with folic acid did not affect seizure incidence, median number of seizure episodes and severity in FH, comparison with H (p > 0.05). The majority of seizure episodes in all groups were of grade 2. There were no significant differences in lethal outcomes at 24 h upon H injection in the FH vs. H group. The activity of Na⁺/K⁺-ATPase and Mg²⁺-ATPase was significantly increased in almost all examined structures in the FH vs. H group. Subchronic folic acid administration did not exacerbate H induced seizures and completely recovered the activity of ATPases.

Spectral analysis of thioacetamide-induced electroencephalographic changes in rats

Thioacetamide (TAA) is widely used as a model of hepatic encephalopathy (HE). The aim of our study was to investigate the effects of TAA on electroencephalographic (EEG) changes in rats and to compare them with human HE. Male Wistar rats were divided into groups: (1) saline-treated group and (2) TAA-treated groups: TAA300 (300 mg/kg), TAA600 (600 mg/kg), and TAA900 (900 mg/kg). Daily dose of TAA (300 mg/kg) was administered intraperitoneally once (TAA300), twice (TAA600), or thrice (TAA900) in subsequent days. EEG changes were recorded about 24 h after the last dose of TAA. Absolute and relative power density in alpha bands were significantly higher in TAA300 versus control group. In TAA300, absolute beta power density was higher and relative beta power density was lower versus control group. Absolute alpha, theta, delta, and relative theta power were significantly lower, while relative power in delta band was significantly higher in TAA900 versus control group (p < 0.01). In conclusion, decrease in EEG voltage with an increase in delta relative power, which correspond to the EEG manifestations of severe HE in humans, was observed in TAA900 group. Electrical activity in TAA300 group correlates with mild HE in humans.

10. Lipid peroxidation as a possible mechanism of acute lindane neurotoxicity in rats

range. We used Student t-test for statistical analysis. Results: In ET patients we recordedM-potential amplitude values of NP (6.77 ± 1.31 mV), which were statistically significantly lower than in CG (8.83 ± 1.64 mV). Other electrophysiological parameters values were not statistically different (p > 0.05) in two groups. Conclusions: ET may have some influence on single ENG parameter values, but most of ENG parameters in patients with ET are in normal ranges. Reduction of NP M-potential amplitude value in patients with ET may be associated with change of motor units function during tremor, chronic fatigue of muscles and other factors.

12. Activity of acetylcholinesterase in acute lindane intoxication in rats

range. We used Student t-test for statistical analysis. Results: In ET patients we recorded M-potential amplitude values of NP (6.77 ± 1.31 mV), which were statistically significantly lower than in CG (8.83 ± 1.64 mV). Other electrophysiological parameters values were not statistically different (p > 0.05) in two groups. Conclusions: ET may have some influence on single ENG parameter values, but most of ENG parameters in patients with ET are in normal ranges. Reduction of NP M-potential amplitude value in patients with ET may be associated with change of motor units function during tremor, chronic fatigue of muscles and other factors.

Dose-dependent anticonvulsive effect of ethanol on lindane-induced seizures in rats

Delta sleep-inducing peptide attenuates severity of lindaneinduced seizures in rats—D. Hrnčić , O. Stanojlović , A. Rašić-Marković , D. Mladenović , T. Radosavljević , D. Vučević , V. Šušić 3 ( Departments of Physiology, School of Medicine, University of Belgrade, Serbia, 2 Department of Pathophysiology, School of Medicine, University of Belgrade, Serbia, 3 Serbian Academy of Sciences and Arts, Serbia)

Phencyclidine analogue metaphit increases body temperature in rats

ior. Video and EEG data were correlated and evaluated through teamwork. Results: Among more than 400 analyzed records from patients with behavior changes, there were 18 with pseudo epileptic seizures: five with epilepsy and non-epileptic attacks, 5 with psychogenic two with hysterical behavior, and three with cardiogenic disturbances and non-epileptic drop attacks. Another group of six patients has had their epileptic seizures misdiagnosed as psychogenic. Conclusions: The gold standard for the diagnosis of non-epileptic seizures is to record multiple characteristic events on the video–EEG and to document apparent impairment of awareness in the absence of epileptiform EEG changes. In case of the large amount of myogenic artifact, video record is more significant, but when there are less or no artifacts, EEG data are diagnostically more contributive.

Post-ictal antinociception effects of audiogenic seizures in metaphit-treated rats

ior. Video and EEG data were correlated and evaluated through teamwork. Results: Among more than 400 analyzed records from patients with behavior changes, there were 18 with pseudo epileptic seizures: five with epilepsy and non-epileptic attacks, 5 with psychogenic two with hysterical behavior, and three with cardiogenic disturbances and non-epileptic drop attacks. Another group of six patients has had their epileptic seizures misdiagnosed as psychogenic. Conclusions: The gold standard for the diagnosis of non-epileptic seizures is to record multiple characteristic events on the video–EEG and to document apparent impairment of awareness in the absence of epileptiform EEG changes. In case of the large amount of myogenic artifact, video record is more significant, but when there are less or no artifacts, EEG data are diagnostically more contributive.