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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.

Background and Objectives: Pilocarpine is used in experimental studies for testing antiepileptic drugs, but further characterization of this model is essential for its usage in testing novel drugs. The aim of our study was to study the behavioral and EEG characteristics of acute seizures caused by different doses of pilocarpine in rats. Materials and Methods: Male Wistar rats were treated with a single intraperitoneal dose of 100 mg/kg (P100), 200 mg/kg (P200), or 300 mg/kg (P300) of pilocarpine, and epileptiform behavior and EEG changes followed within 4 h. Results: The intensity and the duration of seizures were significantly higher in P300 vs. the P200 and P100 groups, with status epilepticus dominating in P300 and self-limiting tonic–clonic seizures in the P200 group. The seizure grade was significantly higher in P200 vs. the P100 group only during the first hour after pilocarpine application. The latency of seizures was significantly shorter in P300 and P200 compared with P100 group. Conclusions: Pilocarpine (200 mg/kg) can be used as a suitable model for the initial screening of potential anti-seizure medications, while at a dose of 300 mg/kg, it can be used for study of the mechanisms of epileptogenesis. [ABSTRACT FROM AUTHOR]

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.

While obesity-related nonalcoholic fatty liver disease (NAFLD) is linked with metabolic dysfunctions such as insulin resistance and adipose tissue inflammation, lean NAFLD more often progresses to liver fibrosis even in the absence of metabolic syndrome. This review aims to summarize the current knowledge regarding the mechanisms of liver fibrosis in lean NAFLD. The most commonly used lean NAFLD models include a methionine/choline-deficient (MCD) diet, a high-fat diet with carbon tetrachloride (CCl4), and a high-fructose and high-cholesterol diet. The major pro-fibrogenic mechanisms in lean NAFLD models include increased activation of the extracellular signal-regulated kinase (ERK) pathway, elevated expression of α-smooth muscle actin (α-SMA), collagen type I, and TGF-β, and modulation of fibrogenic markers such as tenascin-X and metalloproteinase inhibitors. Additionally, activation of macrophage signaling pathways promoting hepatic stellate cell (HSC) activation further contributes to fibrosis development. Animal models cannot cover all clinical features that are evident in patients with lean or obese NAFLD, implicating the need for novel models, as well as for deeper comparisons of clinical and experimental studies. Having in mind the prevalence of fibrosis in lean NAFLD patients, by addressing specific pathways, clinical studies can reveal new targeted therapies along with novel biomarkers for early detection and enhancement of clinical management for lean NAFLD patients. [ABSTRACT FROM AUTHOR]

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]

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.

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.

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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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.

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.

The aim of our study was to investigate the effects of a shortened daily photoperiod on anxiety-like behaviour, brain oxidative stress, lipid status and fatty acid composition of serum lipids in a streptozotocin (STZ)-induced model of diabetes mellitus in rats. Male Wistar rats were divided into the following groups: first group—control group (C12/12); second group—diabetic group (DM12/12; 100 mg/kg STZ); third group—control group exposed to a light/dark cycle 6/18 h (C6/18); fourth group—diabetic group exposed to a light/dark cycle 6/18 h (DM6/18). Anxiety-like behaviour was tested three weeks following STZ injection by elevated plus maze (EPM) and open-field test (OFT). Oxidative stress parameters were measured in the cortex, hippocampus and thalamus, while lipid status and fatty acid methyl esters (FAMEs) were measured in the serum. Both EPM and OFT showed a lower degree of anxiety-like behaviour in the DM6/18 vs. DM12/12 group. Lipid peroxidation in the cortex, hippocampus and thalamus was significantly lower in the DM6/18 vs. DM12/12 group (p < 0.05), associated with an increased level of antioxidant enzymes and protein thiols in the cortex and thalamus. In the DM6/18 group, oleic, vaccenic, dihomo-γ-linolenic and docosahexaenoic acid concentrations were significantly higher in comparison to the DM12/12 group. A shortened daily photoperiod alleviates anxiety-like behaviour in diabetic rats by reduced lipid peroxidation and changes in the serum fatty acids profile. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation in the liver. On the other side, triglyceride and free fatty acid accumulation in hepatocytes promotes insulin resistance via oxidative stress, endoplasmic reticulum stress, lipotoxicity, and the increased secretion of hepatokines. Cytokines and adipokines cause insulin resistance, thus promoting lipolysis in adipose tissue and ectopic fat deposition in the muscles and liver. Free fatty acids along with cytokines and adipokines contribute to insulin resistance in the liver via the activation of numerous signaling pathways. The secretion of hepatokines, hormone-like proteins, primarily by hepatocytes is disturbed and impairs signaling pathways, causing metabolic dysregulation in the liver. ER stress and unfolded protein response play significant roles in insulin resistance aggravation through the activation of apoptosis, inflammatory response, and insulin signaling impairment mediated via IRE1/PERK/ATF6 signaling pathways and the upregulation of SREBP 1c. Circadian rhythm derangement and biological clock desynchronization are related to metabolic disorders, insulin resistance, and NAFLD, suggesting clock genes as a potential target for new therapeutic strategies. This review aims to summarize the mechanisms of hepatic insulin resistance involved in NAFLD development and progression.