scholarly journals NEUROPROTECTIVE EFFECT OF SODIUM NITROPRUSSIDE INTRANASAL ADMINISTRATION ON FUNCTIONAL ACTIVITY OF THE BRAIN AND ANXIETY OF RATS WITH ALCOHOL DEPENDENCE

Author(s):  
Anna Shlіakhova ◽  
Elena Veselovska ◽  
Olga Berchenko ◽  
Anna Titkova ◽  
Elena Prikhodko

Introduction. Disturbances of the molecular nitrosergic mechanisms of brain activity regulation underlie the reduction of brain protective functions under alcohol dependence. However, development of pathogenetically substantiated approaches to the correction of nitrogen oxide (NO) imbalance in the structures of the limbico-neocortical system of the brain (LNCSB) remains insufficient. Objective. To study the effect of intranasal sodium nitroprusside (SNP) administration on anxiety, electrical activity of the LNCSB and NO content in the hippocampus, hypothalamus and septum + nucleus аccumbens of rats with alcohol dependence. Materials and methods. The studies were carried out on 50 nonlinear white adult male rats in a chronic experiment in 3 groups: intact rats; rats with alcohol dependence; rats with alcohol dependence and intranasal SNP administration. The model of alcohol dependence was created by voluntary alcohol intake at a dose of 1.25 g/kg body weight of rat for 35 days. SNP was administered intranasal at a dose of 8 μg/kg body weight of the animal. The level of anxiety was determined by means of neuroethological tests: multi-parameter comprehensive assessment of anxiety, «open field» and «tail suspension test». The electrical activity of LNCSB was registered by the stereotactic introduction of electrodes. The concentration of NO was investigated in the hippocampus, hypothalamus, septum + nucleus аccumbens Results. Intranasal administration of SNP to rats with alcohol dependence led to suppression of convulsive and paroxysmal activity, caused by alcoholization and withdrawal of alcohol, on the electroencephalogram of the structures of the LNCSB and increased the absolute power of biopotentials of the delta and theta ranges on the spectrogram of the hippocampus. Reduction of anxiety was found in rats with a high baseline level of anxiety accompanied by recovery of NO level, which was depleted by chronic alcoholization, in the hypothalamus and hippocampus. Conclusions. Intranasal administration of SNP as a NO donor causes anxiolytic effects in the state of alcohol withdrawal depending on the baseline level of anxiety: in rats with the high baseline level of anxiety – reduces this level; in rats with the low baseline level – restrains it at the level of anxiety after alcohol intake. Intranasal administration of SNP to the rats with alcohol withdrawal causes positive changes in the electroencephalogram of the LNCSB, which are manifested in suppression of convulsive and paroxysmal activity and enhancement of brain biopotentials in alpha and delta ranges on spectrogram of hippocampus with sustaining this effect for whole day. Intranasal administration of SNP is a source of short-term supply of NO to brain cells, which leads to the restoration of NO levels in the hypothalamus, hippocampus, septum and nucleus accumbens – structures that are involved in the regulation of emotional motivational behavior. Key words. limbic-neocortical system of the brain, model of alcohol dependence, anxiety, nitric oxide, sodium nitroprusside

Author(s):  
Olena Veselovska ◽  
Anna Shlyakhova ◽  
Olga Berchenko ◽  
Anna Titkova

The article is addressed to the problem of neuroadaptation in the brain system of emotional reinforcement under alcohol dependence. The level of anxiety, the functional state of the positive emotional reinforcement system, the electrogenesis of the structures of the brain limbic-neocortical system, levels of dopamine in n.accumbens and hypothalamus were studied in an experiment on animals. Particular attention is paid to the transcutaneous allotransplantation of the embryonic hippocampal tissue as a biological approach to suppressing of craving for alcohol intake. It has been shown that allotransplantation reduces alcohol motivation by restructuring of neurophysiological and neurochemical mechanisms in the system of positive reinforcement. Key words: alcohol dependence model, electrical activity of the brain, emotional system of the brain, transcutaneousallotransplantation of embryonic tissue,dopamine


The results of studying the dynamics of clinical and psychopathological manifestations, cognitive disorders, brain electrogenesis in patients with alcohol dependence under the influence of therapy according to the treatment standards (I group) and using the drug "Cereglia" in complex correction (II group) are shown in the work. As a result of treatment revealed positive dynamics of psychopathological symptoms relief in both groups was revealed; in patients II group improving electrogenesis brain manifested a decrease of irritatie, regress polymorphic paroxysmal activity, the representation of slow-wave complexes, normalization of the ratio of alpha- and beta-rhythms, the emergence of regional differences and the reactions of absorption on the functional load clinically manifested by increase of functional activity of the brain and improving cognitive function (improving ability to work and steadfastness of focus, logic of judgments, the correctness and validity of generalizations, processes of semantic memorization, the ability to highlight the main meaning of the perceived material, the ability to analyze, understand and put into words the information received), before the performance standards, the test execution time was significantly shorter in group II patients than in group I patients (p<0.05) and was closer to the test execution time in the control group. It was found that the dynamics of cognitive functions under the influence of treatment is a marker of the degree of manifestations of encephalopathy and evaluation of the effectiveness of therapy with the use of the drug "Cereglia".


2020 ◽  
Vol 1 (14) ◽  
pp. 32-38
Author(s):  
I. Yu. Berezina ◽  
L. I. Sumsky ◽  
A. Yu. Mikhailov ◽  
Yu. L. Arzumanov

Objective: to assess the safety of indicators of electrical activity of the brain for the approach to the analysis of the basic neurophysiological mechanisms of the brain in patients after cardiac arrest.Materials and methods: 52 patients were examined (age — 54,68 ± 19,33) after cardiac arrest. At the time of recording the electroencephalogram (EEG), the level of wakefulness of the examined patients on the Glasgow coma scale was in the range of 3 to 13 points. In 35 patients, EEG recording was performed starting from the first three days from the moment of cardiac arrest, in 17 patients — from the fourth to the 18th day. EEG was registered on electroencephalographs ‘Encephalan–EEGR–19/26’ by ‘Medikom MTD’, ‘Neuron-Spectrum–5/EP’ and ‘Neuron-Spectrum–65’ by ‘Neurosoft’ in accordance with the recommendations of the International Federation of Clinical Neurophysiologists (IFCN). The duration of a single EEG recordings lasted at least 30 min. To localize equivalent dipole sources of pathological activity we used the program ‘BrainLoc 6.0’, (Russia). In 19 patients EEG was recorded in dynamics from 2 to 8 times.Results: all patients showed EEG changes of varying severity, which can be divided into three groups (according to the severity of changes in the EEG: moderate, severe and rough). In the group of patients with gross changes in EEG can be identified 4 variants: the first variant — absence of the alpha rhythm and the dominance of slow-wave fluctuations of the frequency spectrum; variant II — continuous generalized paroxysmal activity; variant III — phenomenon of ‘burst-suppression’; variant IV — a marked decrease in the amplitude of electrical activity of the brain to the level of 2–4 microvolt.Conclusions: based on the dynamics of the EEG pattern in patients after cardiac arrest, it is possible to assume with a certain degree of probability the level of violations in the basic mechanisms of the brain.


2020 ◽  
Vol 11 (4) ◽  
pp. 546-551
Author(s):  
A. M. Titkova ◽  
O. G. Berchenko ◽  
O. V. Veselovska ◽  
A. V. Shliakhova

The role of steroid hormones in regulation of the functions of the emotiogenic limbic-neocortical system has been actively studied over the recent decades in order to determine their synthesis in the brain structures and role in the development and maintenance of dependence on psychoactive substances. However, the wide range of neurosteroids and their metabolites, as well as structural specific features of the synthesis of both neurohormones and their receptors make it difficult to obtain experimental data and interpret the results of the study. The participation of progesterone, cortisol, testosterone and estradiol in the development of alcohol dependence and the changes in their concentrations in the hypothalamus, hippocampus, amygdala and serum under the influence of dosed physical load were studied in 48 outbred adult male rats. Alcohol dependence was modeled by means of consuming food containing alcohol in the dose of 1.25 g of ethanol per 1 kg of rat body weight for two months. Dosed physical load was reproduced by a rat running in a wheel for 30 minutes daily for 7–10 days against the background of alcohol withdrawal. Neuroethological testing of craving for alcohol, EEG recording of the neocortex, hippocampus and amygdala was performed using a computer-diagnostic complex. The concentration of steroid hormones was determined in the structures of the brain and blood serum by the enzyme-linked immunosorbent assay. It was shown that dosed physical load attenuated the alcohol motivation of rats. On the 5th day it suppressed the electrographic manifestations of paroxysmal activity in the hippocampus and increased the level of the theta-rhythm in the amygdala, and on the 7th day it activated the neocortex with increasing beta-rhythm. This effect was accompanied by an increase in serum testosterone level against the background of maintaining functional tension of the peripheral glucocorticoid link of the hypothalamus-pituitary-adrenal system, which was observed in a state of alcohol dependence. The study demonstrated that progesterone plays the key role in allostatic rearrangements of the functional state of animals. An imbalance of progesterone levels was revealed in the brain structures: an increase – in the hypothalamus and hippocampus, and a decrease – in the amygdala under alcohol dependence; a decrease – in the hippocampus with recovery in the amygdala against the background of its high level in the hypothalamus, which occurs under the influence of dosed physical load on the rats under alcohol withdrawal. Thus, the dosed physical load is a promising approach to alcohol dependence rehabilitation.


The complex of neurophysiological methods (stereotaxic implantation of electrodes into brain structures, recording of electrical activity of the neocortex, hippocampus, hypothalamus, and nucleus accumbens) was applied to 65 laboratory male rats with models of chronic alcoholization (during 40 days of alcohol consumption in dose 1.25 g/kg body mass) and alcohol withdrawal during 2 days. The leading role of functional changes of electrogenesis in hippocampus, hypothalamus and nucleus accumbens has been revealed in rats being in states of alcohol dependence. The highest absolute spectral powers of oscillations of the β and Ѳ rhythms in the hippocampus and manifestations of generalized hypersynchronous activity with initiation in the hippocampus and hypothalamus were noted in rats under alcohol dependence. The paroxysmal pattern of activity on EEG of the structures of the limbico-neocortical system acquired an “explosive” character after alcohol withdrawal. The complex of neurochemical methods (detection of dopamine and testosterone concentration with enzymoimmunoassay and nitric oxide concentration with spectrophotometric analysis in the brain structures and serum) was carried out after 40 days of alcoholization as well as after 2 days of alcohol withdrawal. Decreased levels of testosterone and nitric oxide were identified in hypothalamus and hippocampus as well as testosterone in nucleus accumbens and serum. There were observed increased dopamine release in nucleus accumbens in response to latest dose of alcohol consumption and recovery of dopamine level after alcohol withdrawal. To the contrary, the dopamine content decreased in hypothalamus in the state of alcohol withdrawal. The five-time (twice a day) intranasal introduction of sodium nitroprusside repaired nitric oxide and testosterone levels in the brain structures of motivational reinforcement and suppressed seizure pattern on EEG but didn’t change testosterone concentration in serum. Obtained data are considered as one of the important aspects of interactions in the system of hormonal-neurotransmitter-metabolic regulatory mechanisms of motivational reinforcement under formation and suppression of alcohol dependence.


2014 ◽  
Vol 19 (5) ◽  
pp. 3-12
Author(s):  
Lorne Direnfeld ◽  
David B. Torrey ◽  
Jim Black ◽  
LuAnn Haley ◽  
Christopher R. Brigham

Abstract When an individual falls due to a nonwork-related episode of dizziness, hits their head and sustains injury, do workers’ compensation laws consider such injuries to be compensable? Bearing in mind that each state makes its own laws, the answer depends on what caused the loss of consciousness, and the second asks specifically what happened in the fall that caused the injury? The first question speaks to medical causation, which applies scientific analysis to determine the cause of the problem. The second question addresses legal causation: Under what factual circumstances are injuries of this type potentially covered under the law? Much nuance attends this analysis. The authors discuss idiopathic falls, which in this context means “unique to the individual” as opposed to “of unknown cause,” which is the familiar medical terminology. The article presents three detailed case studies that describe falls that had their genesis in episodes of loss of consciousness, followed by analyses by lawyer or judge authors who address the issue of compensability, including three scenarios from Arizona, California, and Pennsylvania. A medical (scientific) analysis must be thorough and must determine the facts regarding the fall and what occurred: Was the fall due to a fit (eg, a seizure with loss of consciousness attributable to anormal brain electrical activity) or a faint (eg, loss of consciousness attributable to a decrease in blood flow to the brain? The evaluator should be able to fully explain the basis for the conclusions, including references to current science.


2021 ◽  
Vol 7 (15) ◽  
pp. eabf6780
Author(s):  
Corinde E. Wiers ◽  
Leandro F. Vendruscolo ◽  
Jan-Willem van der Veen ◽  
Peter Manza ◽  
Ehsan Shokri-Kojori ◽  
...  

Individuals with alcohol use disorder (AUD) show elevated brain metabolism of acetate at the expense of glucose. We hypothesized that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in AUD and that a ketogenic diet (KD) may mitigate these effects. We found that inpatients with AUD randomized to receive KD (n = 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (n = 14). Over a 3-week treatment, KD compared to SA showed lower “wanting” and increased dorsal anterior cingulate cortex (dACC) reactivity to alcohol cues and altered dACC bioenergetics (i.e., elevated ketones and glutamate and lower neuroinflammatory markers). In a rat model of alcohol dependence, a history of KD reduced alcohol consumption. We provide clinical and preclinical evidence for beneficial effects of KD on managing alcohol withdrawal and on reducing alcohol drinking.


1954 ◽  
Vol 190 (6) ◽  
pp. 54-63 ◽  
Author(s):  
W. Grey Walter

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