Functional and biochemical alterations in central nervous system in an experimental model of chronic pelvic pain

Hronični prostatitis/sindrom hroničnog pelvičnog bola (CP/CPPS) je često udružen, nerazjašnjenim mehanizmima, sa poremećajima centralnog nervnog sistema (CNS). Ciljevi ove studije su bili utvrđivanje funkcionalnih i biohemijskih promena koje nastaju u CNS kao posledica CP/CPPS, kao i ispitivanje potencijalnih mehanizama koji dovode do tih promena. Funkcionalno su ispitani podložnost za razvoj konvulzija, prag nocicepcije, ponašanje povezano sa anksioznošću i depresijom i kognitivne sposobnosti. Biohemijskim ispitivanjem obuhvaćeni su parametri redoks statusa i nivo proinflamatornih citokina i ICAM-1 u strukturama mozga, kao i nivo testosterona i kortikosterona u serumu. Imunohistohemijski je ispitan proces neurogeneze i gliogeneze u hipokampusu. Ispitivani su i potencijalni terapijski efekti modulacije nivoa gasotransmitera CO i hronične aerobne fizičke aktivnosti u ovom modelu. Životinje sa eksperimentalnim CP/CPPS su razvile hiperekscitabilnost CNS, ali su povećano ispoljavale ponasanje povezano sa anksioznos ću i depresijom, kao i kognitivnu disfunkciju. U hipokampusu, talamusu i korteksu zivotinja sa CP/CPPS doslo je do pojave oksidativnog stresa, a nivo proinflamatornih citokina IL-β i IL-6 i ekspresija ICAM-1 bili su povećani u talamusu i korteksu, sto ukazuje na neuroinflamaciju. Razvoj CP/CPPS je doveo do hormonskog disbalansa, u vidu povećanja kortikosterona i smanjenja testosterona u serumu. Adultna neurogeneza je bila smanjenog, a gliogeneza povećanog obima u hipokampusu, gde je utvrđen i smanjen broj inhibitornih interneurona. Hronicni aerobni trening i CORM A1, donor CO, imali su antinociptivno, anksiolitic ko, antidepresivno, antiinflamatorno i antikonvulzivno dejstvo u modelu CP/CPPS, sto ukazuje na njihove potencijalne terapijske efekte.Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is often associated with central nervous system (CNS) disorders by unelucidated mechanisms. The aims of this study were to determine the functional and biochemical changes in the CNS induced by CP/CPPS, as well as the potential underlying mechanisms. Functional study included assessment of seizure susceptibility, nociception threshold, anxiety- and depression-like behavior, and cognition. The biochemical analyses consisted of assessment of redox status parameters, pro-inflammatory cytokines, and ICAM-1 expression in the brain structures, and the concentration of testosterone and corticosterone in the serum. The process of hippocampal neurogenesis and gliogenesis were examined immunohistochemically. The potential therapeutic effects of the CO gasotransmitter level modulation and chronic aerobic physical activity in this model were also investigated. Animals with experimental CP/CPPS developed CNS hyperexcitability, increased anxiety- and depression-like behavior, as well as cognitive impairment. Oxidative stress occurred in the hippocampus, thalamus, and cortex of animals with CP/CPPS, and the level of proinflammatory cytokines IL-β and IL-6, and ICAM-1 expression were increased in the thalamus and cortex, indicating neuroinflammation. Hormonal imbalance, as an increase in corticosterone and a decrease in serum testosterone concentration, was observed. Adult neurogenesis was reduced, while gliogenesis was increased in the hippocampus, and the lower number of hippocampal inhibitory interneurons was also found. Chronic aerobic training and CORM A1 (CO releasing molecule) had antinociceptive, anxiolytic, antidepressant, anti-inflammatory and anticonvulsant effects in the CP/CPPS model, indicating their potential therapeutic effects

Glial cells, blood brain barrier and cytokines in seizures: Implications for therapeutic modalities

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

Exploratory behavior alteration as an epileptic comorbidity in elevated plus maze test

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

Basic characteristics of epileptiform discharges triggered by lindane 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

Shortened Daily Photoperiod Alleviates Anxiety-like Behaviour by Antioxidant Effect and Changes Serum Fatty Acid Profile in Diabetic Rats

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

The effect of light/dark cycle changes on vascular permeability, inflammation and visual cycle in streptoyotocin-induced diabezic retinophaty in rats

Introduction: Diabetic retinopathy (DR) is not cured efficiently and changes of lifestyle measures may alleviate its course. The aim of our study was to investigate the effects of shortened daily photoperiod on inflammation and visual cycle in rat retina and retinal pigment epithelium (RPE) in DR. Methodology: Male Wistar rats were divided into the following groups: 1. control; 2. diabetic group (DM) treated with a single intraperitoneal injection of streptozotocin (100 mg/kg); 3. group exposed to light/dark cycle 6/18h for 3 months (6/18); 4. diabetic group exposed to light/dark cycle 6/18h (DM+6/18). Retinal blood vessel permeability was estimated immunohistochemically based on lectin staining, while the expression of genes involved in the visual cycle (SOX9, LRAT, RPE65, OTX2), and inflammation (IL-1, TNF-α) was determined by qRT-PCR in the retina and RPE. Results: Shortened photoperiod reduced neovascularisation and the expression of IL-1 and TNF-α in both retina and RPE. The expression of IL-1 and TNF-α genes in the retina was significantly higher in DM vs. control group (P=0.001). In contrast, retinal IL-1 and TNF-α expressions were significantly lower in DM+6/18 vs. DM group (P=0.001). The expression of IL-1 and TNF-α in RPE was significantly higher in DM vs. control group, however the expression of these genes was significantly lower in DM+6/18 vs. DM group (PIL-1=0.008 and PTNF-α=0.002). The expression of visual cycle genes was significantly up-regulated in RPE in DM+6/18 vs. DM group (P=0.001). Conclusion: Shortened daily photoperiod reduces blood vessel permeability in DR via its anti-inflammatory effect associated with accelerated visual cycle in the retina.Poster Session: Neuroimmunoendocrine Interaction

Functional and biochemical alterations in central nervous system in an experimental model of chronic pelvic pain

Hronični prostatitis/sindrom hroničnog pelvičnog bola (CP/CPPS) je često udružen, nerazjašnjenim mehanizmima, sa poremećajima centralnog nervnog sistema (CNS). Ciljevi ove studije su bili utvrđivanje funkcionalnih i biohemijskih promena koje nastaju u CNS kao posledica CP/CPPS, kao i ispitivanje potencijalnih mehanizama koji dovode do tih promena. Funkcionalno su ispitani podložnost za razvoj konvulzija, prag nocicepcije, ponašanje povezano sa anksioznošću i depresijom i kognitivne sposobnosti. Biohemijskim ispitivanjem obuhvaćeni su parametri redoks statusa i nivo proinflamatornih citokina i ICAM-1 u strukturama mozga, kao i nivo testosterona i kortikosterona u serumu. Imunohistohemijski je ispitan proces neurogeneze i gliogeneze u hipokampusu. Ispitivani su i potencijalni terapijski efekti modulacije nivoa gasotransmitera CO i hronične aerobne fizičke aktivnosti u ovom modelu. Životinje sa eksperimentalnim CP/CPPS su razvile hiperekscitabilnost CNS, ali su povećano ispoljavale ponasanje povezano sa anksioznos ću i depresijom, kao i kognitivnu disfunkciju. U hipokampusu, talamusu i korteksu zivotinja sa CP/CPPS doslo je do pojave oksidativnog stresa, a nivo proinflamatornih citokina IL-β i IL-6 i ekspresija ICAM-1 bili su povećani u talamusu i korteksu, sto ukazuje na neuroinflamaciju. Razvoj CP/CPPS je doveo do hormonskog disbalansa, u vidu povećanja kortikosterona i smanjenja testosterona u serumu. Adultna neurogeneza je bila smanjenog, a gliogeneza povećanog obima u hipokampusu, gde je utvrđen i smanjen broj inhibitornih interneurona. Hronicni aerobni trening i CORM A1, donor CO, imali su antinociptivno, anksiolitic ko, antidepresivno, antiinflamatorno i antikonvulzivno dejstvo u modelu CP/CPPS, sto ukazuje na njihove potencijalne terapijske efekte.Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is often associated with central nervous system (CNS) disorders by unelucidated mechanisms. The aims of this study were to determine the functional and biochemical changes in the CNS induced by CP/CPPS, as well as the potential underlying mechanisms. Functional study included assessment of seizure susceptibility, nociception threshold, anxiety- and depression-like behavior, and cognition. The biochemical analyses consisted of assessment of redox status parameters, pro-inflammatory cytokines, and ICAM-1 expression in the brain structures, and the concentration of testosterone and corticosterone in the serum. The process of hippocampal neurogenesis and gliogenesis were examined immunohistochemically. The potential therapeutic effects of the CO gasotransmitter level modulation and chronic aerobic physical activity in this model were also investigated. Animals with experimental CP/CPPS developed CNS hyperexcitability, increased anxiety- and depression-like behavior, as well as cognitive impairment. Oxidative stress occurred in the hippocampus, thalamus, and cortex of animals with CP/CPPS, and the level of proinflammatory cytokines IL-β and IL-6, and ICAM-1 expression were increased in the thalamus and cortex, indicating neuroinflammation. Hormonal imbalance, as an increase in corticosterone and a decrease in serum testosterone concentration, was observed. Adult neurogenesis was reduced, while gliogenesis was increased in the hippocampus, and the lower number of hippocampal inhibitory interneurons was also found. Chronic aerobic training and CORM A1 (CO releasing molecule) had antinociceptive, anxiolytic, antidepressant, anti-inflammatory and anticonvulsant effects in the CP/CPPS model, indicating their potential therapeutic effects

Glial cells, blood brain barrier and cytokines in seizures: Implications for therapeutic modalities

info:eu-repo/semantics/publishe

The central nervous system is not imunoprivileged: Inflammation and epileptogenesis

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