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Epilepsy is one of the leading neurological disorders and affects 1-2% of the world’s population. Generally, it is a result of an imbalance between excitatory and inhibitory phenomena in the central nervous system (CNS), but the mechanisms of its initiation and propagation still require further investigations. Experimental models represent one of the most powerful tools to better understand the mechanisms of epileptogenesis. Nitric oxide (NO) is gaseous molecule with pleiotropic physiological and pathological effects in almost all organ systems and intriguing biological relevance, especially in the CNS where it acts as a gaseous neurotransmitter. The role of NO in the generation of epilepsy is highly contradictory, since there is evidence of its anticonvulsive, as well as proconvulsive properties. Therefore, we will discuss in this review the involvement of NO-mediated signaling pathways in the mechanisms of epileptogenesis, taking into account the findings revealed in experimental studies on animal models of epilepsy. [Acknowledgments. This study was supported by Ministry of Education and Science of Serbia, Grant No. 175032]

Although there is still no ideal experimental model of hepatic encephalopathy, thioacetamide is widely used for the induction of acute and chronic liver failure. Thioacetamide exerts hepatotoxic effects through the formation of toxic metabolites in hepatocytes, oxidative stress and calcium mobilization. An ideal experimental model of hepatic encephalopathy should have similar behavioral and electroencephalographic manifestations as human encephalopathy. Thioacetamide induces motor manifestations in a dose-dependent manner. Milder forms of thioacetamide-induced encephalopathy are associated with an increase in relative alpha power, while more severe forms are followed by a flattening of the electroencephalogram. liver failure-induced hyperammonemia has a pivotal role in the neurotoxic effects of thioacetamide. Hyperammonemia induces brain edema, alterations in neurotransmission, oxidative stress, mitochondrial dysfunction and neuronal death. The aim of this article is to review the behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy, as well as to summarize potential mechanisms involved in thioacetamide neurotoxicity.[Acknowledgments. This work was supported by the Ministry of Education and Science of Serbia, Grant No 175032]

Introduction: Chronic prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is the most commonly diagnosed non-infectious prostatitis in urology. Studies have shown that CP/CPPS can induce neuroinflammation, which may result in CNS hyperexcitability and a tendency to develop epileptic seizures. Spike salvos are ictal EEG graph elements typical for the experimental model of lindane-induced seizures. There are a number of mathematical models for quantitative analysis of EEG, including the Fast Fourier Transform (FFT). It transforms the signal from time into the frequency domain, providing information on Power Spectral Densities (PSD). Aim: The aim of this study was to investigate the basic characteristics of epileptiform discharges induced by subconvulsive dose of lindane in rats, with experimentally induced CP/CPPS. Material and methods: CP/CPPS was induced by intraprostatic injection of 3% l-carrageenan in male Wistar albino rats. Animals with CP/CPPS were implanted with EEG registration electrodes, and then administered lindane (4 mg/kg, i.p, experimental group, n = 6 per group) or its solvent (DMSO, control group, n = 6 per group). An 8-channel EEG device was used in combination with software developed in the laboratory (NeuroSciLaBG). Ictal EEG epochs were extracted from the original signal and FFT analysis was performed to obtain information taking into account PSD in predefined frequency bands. Results: There was no ictal activity in the EEG of control animals. In experimental animals, ictal activity occurred and the mean duration of the ictal period was 2.06 s. FFT analysis revealed that the Alpha frequency range (7-15 Hz) was markedly dominant during ictal activity. Conclusion: The results of this study showed the characteristics of epileptiform discharges in animals with experimentally induced CP/CPPS. This study and animal model are suitable for future translational studies of the comorbidities of this syndrome.

Emotions are specific psychological states brought about by neurophysiological changes associated with feelings, thoughts and behavioral responses. Emotions were considered as irrational experiences beyond the domain of logical perception because of their intertwinement with mood, temperament, creativity, motivation and personality. Through the centuries, emotions have been the focus of research among great classical philosophers, doctors, neuropsychologists, neuroscientists, neurologists and psychiatrists. The neurophysiological basis of behavior, such as emotional facial expression, and autonomic events in the physiological theory of William James and James-Lange and modified by Cannon-Bard, was followed by the two-factor theory of emotions of Schachter-Singer and Lazarus’ higher-order cognitive evaluation. Four components that influence each other represent the concept of emotions and complete the overall emotional experience, and these are: autonomous (increase in heart rate, blood pressure); somatic (body language, facial expressions); cognitive (control, management), and subjective feeling (emotion, individual experience). The interplay between emotions and cognition has been the subject of research. Emotions can be evoked reflexively by simple physical stimuli (bottom-up), but can also be complex reactions involving cognitive, physiological and behavioral reactions (top-down). The amygdala, the “alert" or “neural alarm” structure, is responsible for conditioning fear, while the medial prefrontal cortex participates in emotion self-regulation and decision making.

Lindane-induced seizure in rats is a model of refractory generalized epilepsy. Hydrogen sulfide (H2S) is a gasotransmitter with different physiological and pathological roles. Cystathionine-β-synthase (CBS) is a major enzyme responsible for H2S production in the brain. The aim of this study was to investigate the effects of H2S production inhibition using aminooxyacetate (a CBS inhibitor) on behavioral and EEG manifestations of lindane-induced seizures. Male Wistar rats with previously implanted EEG electrodes were intraperitoneally (i.p.) treated with 4 mg/kg lindane and observed for convulsive behavior and EEG manifestations during the next 30 min. Aminooxyacetate (5, 15 and 25 mg/kg, i.p.) or saline, was injected 30 min prior to lindane. Convulsive behavior was assessed by seizure incidence, latency time and severity (grades 0-4). The number and duration of ictal periods in the EEG were also analyzed. Seizure incidence was higher in rats treated with aminooxyacetate (AOA) before lindane, but not significantly when compared with those treated only with lindane. However, AOA significantly decreased the latency time and augmented the severity of lindane-induced seizures in a dose-dependent manner. EEG analysis revealed an increased number and duration of ictal periods in rats receiving AOA prior to lindane. H2S production inhibition aggravated lindane-induced seizures, which showed a functional relationship between H2S and the effects of lindane.

Introduction: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases of genitourinary system in male population. It is frequently accompanied by psychosocial disorders which include anxiety. Despite numerous clinical studies, the mechanisms of this link are still unclear, partly due to the lack of studies on experimental animal models. Aim: The aim of this study was to examine locomotion activity and anxiety in rats, with experimentally induced CP/CPPS, using the open field test. Material and methods: Wistar male rats were randomly distributed into control and experimental group. In experimental group, CP/CPPS was induced by single intraprostatic injection of 3% l-carrageenan. Development of pelvic pain syndrome was assessed by evaluating mechanical pain thresholds by electronic von Frey aesthesiometer (eVF). The rats were individually tested in the open field, seventh day following the intraprostatic injection. Results: In animals from the experimental group, distance and time of ambulatory movement in the open field test were significantly decreased, number of rearing reduced, time spent in the center of the open field significantly decreased, while index of thigmotaxis was significantly increased compared to the control animals. Conclusion: Results of this study indicate anxiogenic effect of CP/CPPS in rats.

Lindane is a scabicide and pesticide that can exert neurotoxic effects such as tonic and clonic seizures that are refractory to many antiepileptic drugs. Folic acid stands out as a potential substance worth testing for its neuroprotective and in certain experimental models anticonvulsive effects. The aim of the present study was to examine the potential therapeutic value of folic acid supplementation on the behavioral characteristics of lindane-induced seizures. Adult male Wistar rats were divided into the following groups: Controls: dimethyl sulfoxide-injected (C1), saline-treated (C2); lindane (4 mg/ kg; 6 mg/kg; 8 mg/kg; L4; L6; L8, respectively); folic acid 15 mg/kg (F) and F administered 30 min prior to L4, L6, or L8 (L4F; L6F; L8F, respectively). Convulsive behavior was assessed by the incidence of seizures, seizure latency and seizure severity. Lindane administration has shown a tendency of proportional increase in seizure incidence, decrease in seizure latency and increase in seizure intensity. Pretreatment with folic acid significantly prolonged the latency period and decreased the frequency of grade 4 seizures in the L8F group when compared to the L8 group. We concluded that folic acid alleviates the behavioral manifestations of lindane-induced seizures and that it can be applied as a potential adjuvant in lindane-poisoned patients; however, further research is still needed. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175032]

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. [ABSTRACT FROM AUTHOR]

Epilepsy is a very prevalent neurological disorder. The gold standard in diagnosis of epilepsy is the EEG signal recorded during a seizure with characteristic ictal pattern. Automated systems for detection of seizures are a field of intensive research, in an attempt to create a reproducible, observer-independent mechanism for epilepsy diagnosis. Chronic therapy is a cornerstone of the epilepsy treatment, but the possibility to predict seizure onset and, consequently, to act with medications right before the seizure, instead of relying on everyday medications, is considered the holy grail of epilepsy research. Significant element of morbidity and mortality in epilepsy is sudden unexpected death in epilepsy (SUDEP) that occurs in roughly 1% of patients. Signal analysis techniques for EEG have been a staple in epilepsy research, but recently, with the rise of telemetric systems, heart rate variability (HRV) analysis derived from the ECG signal has been gaining importance. It has been found that perturbations in autonomic nervous system (ANS) regulation occur during, and even up to several minutes before, seizure onset allowing for changes in HRV to act in prediction, as well as detection, of seizures. Also, there is a compelling research exploring the extent of autonomic disbalance during seizures, as well as in the interictal periods in patients at risk for or that have had SUDEP. The focus of this review is to give a short crossection of research involving the utility HRV has in prediction and detection of seizure onset, as well as determining etiology classification and risk evaluation in SUDEP.

Introduction: EEG is a widely used method of epilepsy examination. In order to quantitatively inspect ictal EEG findings, a number of mathematical models have been developed over the years, one of them being the Fast Fourier Transform (FFT). It transforms the signal from time domain into frequency domain, giving information about their power spectral densities (PSD). Lindane is a well-established neurotoxic agent often used in experimental studies as a model of generalized epilepsy. This study aims to quantitatively examine the characteristics of ictal EEG activity in rats on model of generalized epilepsy induced by lindane. Materials and Methods: Wistar albino rats were used for the study. Electrodes were surgically implanted over the frontal, parietal and occipital cortices of each animal for EEG recording purposes prior to lindane administration in convulsive dose. An 8-channel EEG apparatus was used, combined with a software developed in the Laboratory (NeuroSciLaBG). Ictal EEG epochs were extracted from the original signal and FFT analysis performed to obtain information considering PSD in predefined frequency bands. Amplitude histogram feature of the software was used to differentiate ictal spikes based on their voltage. Results: FFT analysis has yielded important information regarding spectral powers in frequency domain. Ictal EEG showed considerable stratification, theta frequency band (4-7 Hz) being markedly dominant. Amplitude histogram showed the majority of spikes to be in the voltage ranges up to 250 μV, while higher voltage spikes were rarely observed. Conclusion: FFT is capable of giving important information about ictal period characteristics. Ictal periods induced by lindane are characterized by dominancy of theta rhythm and spiking activity mostly in amplitude bins up to 250 μV. FFT and amplitude histograms can be of critical importance in the future pharmacological and toxicity studies.

Epilepsy is a chronic, common, neurological disorder marked by transient, paroxysmal and hypersynchronous activity of the brain neurons, behaviorally manifested as seizures. It is developed through the process of epileptogenesis which alters neuronal excitability, establishes critical interconnections and develop neuronal hyperexcitability and degeneration, as well as the neuronal network reorganization as its main mechanisms. There are a number of different mechanisms of epileptogenesis, including neuroinflammation as a recently highlighted important novel mechanism. In this review paper, our focus will be to light up the latest findings about neuroinflammation as a pathogenic factor in epileptogenesis. Neuroinflammation is characterized by the structural and functional alteration of the CNS glial cells and peripherally derived immune cells with the presence of blood-brain barrier (BBB) dysfunction as main mechanisms. Disequilibrium in the CNS microenvironment is often followed by increased synthesis of proinflammatory cytokines (IL-6, IL-1β, TNF-α, IFN-γ) and chemokines. The interplay between glial alteration, BBB dysfunction, cytokines and chemokines establish a positive feedback cascade for further epileptogenesis. It is still unclear if neuroinflammation is causing epileptogenesis or whether in a consequence of that, but, there are clear findings about positive feedback between these two processes. This interconnection could be a helpful key to better target therapeutic treatment of neuroinflammation for providing beneficial effects for patients with epilepsy.

Delta sleep-inducing peptide (DSIP) is an endogenous peptide that is constantly present in several different brain regions. Lindane is used as a pesticide and scabicide, but it also induces seizures refractory to conventional antiepileptics. The aim of this paper was to determine whether DSIP modulates lindane-induced seizures in rats in a behavioral and electroencephalographic (EEG) study. DSIP (1 mg/kg, i.p.) or dimethyl-sulfoxide (DMSO, 0.5 ml/kg, intraperitoneally (i.p.)) were injected 30 min before lindane (8 mg/kg, i.p.) to adult male rats with previously implanted electrodes for EEG registration. During the following 30 min, the EEG was registered, and the following behavioral characteristics of seizures were observed: incidence, latency and intensity. A descriptive scale with grades from 0 to 4 provided an estimate of seizure intensity. In the EEG, the number and duration of ictal periods were analyzed using NeuroSciLaBG (Belgrade, Serbia) software. The lethality rate was also analyzed. DSIP-treated animals showed significantly modified characteristics of lindane-induced seizures when compared to the group without DSIP pretreatment (i.e. a reduced seizure intensity and a prolonged seizure latency period). However, no significant effects of DSIP on seizure incidence and lindane-induced lethality were observed. EEG analyses showed a significantly decreased number of lindane-induced EEG ictal periods in DSIP-treated animals, but with unaltered duration. These results show that DSIP favorably modulates lindane-induced seizures in rats, showing a potential to be an adjuvant component of antiepileptic treatment strategy for refractory seizures. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175032]

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Sleep represents physiological process which effects are crucial to maintain homeostasis. Sleep disturbances are widely spread within the population worldwide. The loss in quantity or quality of sleep is associated with numerous diseases. Also, sleep disturbances are highly connected to depressive disorders, but exact mechanism of this interaction still remains unknown. Understanding the underlying mechanisms could be the key for treatment of both disorders especially in patients with psychosomatic and psychiatric comorbidities. Therefore, in this article, we will summarize the most recent findings on the connection between sleep disturbances and depressive disorders, including the mechanisms of this interaction.

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. [ABSTRACT FROM AUTHOR]

Introduction: Epileptic seizure consists of preictal, ictal and postictal period. Postictal period is characterized by a variety of psychiatric phenomenon of which the most frequent ones are anxiety and depressive disorder. Anxiety in rodents can be assessed by measuring the exploratory behavior. Lindane evokes generalized tonic-clonic epileptic seizures in rats, when applied intraperitoneally, due to its lypophilic characteristics. Aim: The aim of this study was to assess exploratory behavior linked with anxiety level in the elevated plus maze test (EPM) upon generalized seizures, induced by lindane in male rats. Material and methods: The experiment was conducted on Wistar albino male rats that were randomly divided into: control group (DMSO, 0.5 ml/kg) and experimental group (lindane, 8 mg/kg) (n=8, each). After the drug injection, the assessment of the seizure intensity lasted for 30 minutes. Descriptive rating scale was used to describe the seizure severity. Subsequently, the EPM testing took place immediately after evoking the seizure (Test 1), after 1h (Test 2) and after 24h (Test 3). Time spent in open areas and number of transitions was further analyzed. Results: Experimental group of animals spent less time in open areas of EPM, when compared to controls in Test 1 and Test 2. The same holds true for the number of transitions to the open area, i.e. lindane-treated animals tend to stay in enclosed parts of the maze in Test1, Test 2. Finally, in Test 3 there was no significant difference between the groups, in any parameter of interest. Conclusion: Lindane-induced generalized epileptic seizures are accompanied by reduced exploratory behavior in the elevated plus maze test, up to 24h after the seizure ended. This finding can be a basis for the further translational research of anxiety as epileptic comorbidity in this experimental model of epilepsy.

Introduction. A single coronary artery (SCA) is defined as a coronary artery that arises from the sinus of Valsalva and supplies the entire heart. This is a rare congenital anomaly occurring in approximately 0.04–0.13% of the population. SCA can be diagnosed during life by coronary angiography and multislice cardiac computed tomography. There are many anatomical variations of single coronary arteries. Case outline. A 50-year-old man presented with acute ST elevation myocardial infarction (STEMI). Coronary angiography revealed the case of an SCA with left anterior descending artery and circumflex artery arising separately from the right coronary artery which was occluded proximally to their taking-off. Successful primary percutaneous coronary intervention was performed and is reported here in details. This is the first described case of an SCA (classified as R-III and R-III-C by Lipton and Yamanaka, respectively) with a clinical presentation as STEMI. A description of the undertaken management is also provided. Conclusion. Coronary artery anomalies require accurate recognition in order to help cardiologists plan appropriate management of these patients.

[Projekat Ministarstva nauke Republike Srbije, br. 175032]