Alterations of medial prefrontal cortex bioelectrical activity in experimental model of isoprenaline-induced myocardial infarction

Background Clinical and animal studies have found that anxiety and depression are significantly more common after acute myocardial infarction (AMI). The medial prefrontal cortex (PFC) has a dual role: in higher brain functions and in cardiovascular control, making it a logical candidate for explaining the perceived bidirectional heart-brain connection. We used parallel Electrocardiography (ECG) and Electrocorticography (ECoG) registration to investigate AMI-induced changes in medial PFC bioelectrical activity in a rat model of AMI. Materials and methods Adult male Wistar albino rats were used in the study. Gold-plated recording electrodes were implanted over the frontal cortex for ECoG recording. ECG was recorded via two holter electrodes attached on the skin of the back fixed in place by a jacket. Induction of AMI was performed by isoprenaline (150 mg/kg, i.p.). ECoG and ECG signals were registered at baseline, during 3 hours after isoprenaline administration and at 24 hours after isoprenaline administration. Results Significant increases of theta, alpha, and beta electroencephalographic (EEG) band power were observed in different time intervals after isoprenaline administration. Significant increase of theta band peak frequency was also observed during the first hour after isoprenaline administration. No statistically significant differences in band-power activity were found between the pre-isoprenaline measurements and 24 hours after administration. Conclusion Our results demonstrate significant increases in EEG band power of alpha beta and theta bands during isoprenaline-induced AMI model. These are the first findings to connect heart damage during isoprenaline- induced AMI to disturbances in the cortical bioelectrical activity. © 2020 Vorkapić et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The study was supported by Ministry of Science Education and Technological Development of Serbia, Grant No. 175032 and 175016. The TECNALIA provided support in the form of salary for author MI, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the ‘author contributions’ section. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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

Gojaznost i reproduktivna funkcija žene - mehanizmi nastanka i terapijske implikacije

Gojaznost se danas smatra uzrokom nastanka kardiovaskularne bolesti, tipa 2 dijabetesa, osteoartritisa, maligniteta, ali i faktorom koji doprinosi nastanku reproduktivnih poremećaja i problema plodnosti. Postoji povećan relativni rizik za nastanak anovulatornog infertiliteta u žena sa izraženom gojaznošću i produženo vreme do koncepcije. U žena u reproduktivnom periodu gojaznost je povezana sa povećanim rizikom za nastanak hiperandrogenizma i anovulacije, kao što je slučaj u sindromu policističnih jajnika (PCOS) kao najčešćem hiperandrogenom poremećaju. Postoji veliki broj dokaza u prilog postojanja bliskog odnosa adipokina, gojaznosti, metaboličkog sindroma i reproduktivnih posledica. Redukcija težine za 5-10% dovodi do poboljšanja u kliničkim, metaboličkim i reproduktivnim karakteristikama, kao što je slučaj u žena sa PCOS. Primena insulinskih senzitajzera vodi sniženju hiperinsulinemije, insulinske rezistencije, uspostavljanju normalne menstrualne cikličnosti i ovulacije kod značajnog broja žena sa PCOS. Gojaznost može uticati na stimulaciju ovulacije njenim produžavanjem, povećanjem doze gonadotropina, incidence folikularne asinhronije i prekida stimulacije. Hirurško lečenje gojaznosti predstavlja alternativni vid terapije u slučaju kada ni promena načina života ni farmakoterapijske mere ne daju povoljne rezultate. Za sada ne postoji dovoljno dokaza u prilog preporuke da se barijatrijska hirurgija koristi u lečenju gojaznih žena sa PCOS.Projekat ministarstva br. 175032 i br. 4100

Gojaznost i reproduktivna funkcija žene - mehanizmi nastanka i terapijske implikacije

Gojaznost se danas smatra uzrokom nastanka kardiovaskularne bolesti, tipa 2 dijabetesa, osteoartritisa, maligniteta, ali i faktorom koji doprinosi nastanku reproduktivnih poremećaja i problema plodnosti. Postoji povećan relativni rizik za nastanak anovulatornog infertiliteta u žena sa izraženom gojaznošću i produženo vreme do koncepcije. U žena u reproduktivnom periodu gojaznost je povezana sa povećanim rizikom za nastanak hiperandrogenizma i anovulacije, kao što je slučaj u sindromu policističnih jajnika (PCOS) kao najčešćem hiperandrogenom poremećaju. Postoji veliki broj dokaza u prilog postojanja bliskog odnosa adipokina, gojaznosti, metaboličkog sindroma i reproduktivnih posledica. Redukcija težine za 5-10% dovodi do poboljšanja u kliničkim, metaboličkim i reproduktivnim karakteristikama, kao što je slučaj u žena sa PCOS. Primena insulinskih senzitajzera vodi sniženju hiperinsulinemije, insulinske rezistencije, uspostavljanju normalne menstrualne cikličnosti i ovulacije kod značajnog broja žena sa PCOS. Gojaznost može uticati na stimulaciju ovulacije njenim produžavanjem, povećanjem doze gonadotropina, incidence folikularne asinhronije i prekida stimulacije. Hirurško lečenje gojaznosti predstavlja alternativni vid terapije u slučaju kada ni promena načina života ni farmakoterapijske mere ne daju povoljne rezultate. Za sada ne postoji dovoljno dokaza u prilog preporuke da se barijatrijska hirurgija koristi u lečenju gojaznih žena sa PCOS.Projekat ministarstva br. 175032 i br. 4100

Behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy: Possible mechanisms of neurotoxic effects

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

Behavioral and electroencephalographic effects of delta sleep inducing peptide and its analogue on metaphit-induced audiogenic seizures in rats

INTRODUCTION Delta sleep inducing peptide (DSIP) is well known natural somnogenic peptide that has many other physiological functions. DSIP analogues representing hepta-and octapeptides (also known as long) as well as tetrapeptide (termed short, used in our experiments) were synthesized with a view to evaluate the peptide specificity in sleep. The effects of DSIP and its analogue DSIP1-4 on metaphit 1-[1(3-isothiocyanatophenyl-ciclohexyl)-piperidine] induced audiogenic seizures were evaluated in rats. METHODS Male Wistar albino rats were divided into 4 groups: 1. Saline; 2. Metaphit; 3. Metaphit + DSIP, and 4. Metaphit + DSIP1-4. To examine the blocking effects of DSIP and its analogue on fully developed metaphit seizures, the last two groups were injected after the 8th audiogenic testing. Animals were injected with metaphit (10 mg/kg) intraperitoneally (i.p.) and exposed to sound stimulation (100±3 dB, 60 s) at hourly intervals. The incidence and severity (running, clonus and tonus) of seizures were analyzed. For electroencephalographic (EEG) recordings, three gold-plated electrodes were used. Convulsive behavior was assessed by incidence of motor seizure and by seizure severity grade, determined by descriptive rating scale ranging from 0 to 3:0- no response, 1 -wild running only; 2-wild running followed by clonic seizures of all four limbs with body rollover; 3 - wild running progressing to generalized clonic convulsions followed by tonic extension of fore-and hind legs and tail. Sound onset, seizure events, and sound offset, along with the animal's behavior (convulsive or other) were characterized with EEG changes. RESULTS In most animals, the administration of metaphit resulted in electroencephalographic abnormalities, elicited epileptic-form activity in the form of spikes, polyspikes and spike-wave complexes. Maximum incidence and severity of metaphit convulsions occurred 8 h after the injection (9/12, 75%), then abated gradually and disappeared 30 h later. Both DSIP and DSIP1-4 significantly increased the power spectra of d waves and decreased the incidence of seizures, mean seizure grade and tonic component of metaphit-induced convulsions. DISCUSSION Metaphit has been shown to induce audiogenic seizures after systemic and intracerebroventricular administration and to be truly epileptic in small rodents [8-11], although about 8 h after metaphit administration, the power spectra increased and was more intense in the period of sound onset and seizure events. Taken together, DSIP makes an optimal ratio between inhibitory and excitatory amino acid neurotransmitters and may represent one of the endogenous control systems of the brain, thus exerting the protective effect against the seizures [14,15,19]. The results obtained throughout the present study corroborate and broaden the data on prolonged antiepileptic DSIP effect. CONCLUSION The results of the present study strongly suggest that treatment of adult rats with DSIP and its analogue DSIPM should be considered as potential natural antiepileptics

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: 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)), or thrice (TAA(900)) 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 TAA(300) versus control group. In TAA(300), 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 TAA(900) versus control group (p LT 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 TAA(900) group. Electrical activity in TAA(300) group correlates with mild HE in humans