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Biomedical subjects

M Koupilová

Publications and source records attributed to M Koupilová.

At least 19 recordsLinked to original sources
PubMed2001

The influence of low-level sarin inhalation exposure on spatial memory in rats.

To study the influence of low-level sarin exposure on cognitive functions, the rats were exposed to three various low concentrations of sarin (Levels 1-3) for 60 min in the inhalation chamber. In addition, one group of rats was exposed to Level 2 of sarin repeatedly. Testing of cognitive functions was carried out using the Y-maze evaluating learning and spatial memory. The correct averse behavior of sarin-exposed rats in the Y-maze was tested several times within 6 weeks following sarin inhalation exposure to look for any cognitive impairments. The results were compared to the Y-maze performance of control rats exposed to pure air instead of sarin. While a subtle and short-term deficiency in the Y-maze performance was observed in rats exposed to the Levels 1 and 2 of sarin, the exposure to the Level 3 of sarin caused a significant decrease in the Y-maze performance for a relatively long time. Similar sarin-induced spatial memory impairments were demonstrated in rats exposed repeatedly to the Level 2. A decrease in the Y-maze performance was observed until the end of the third week following the last exposure to sarin. Thus, our findings confirm that both nonconvulsive symptomatic and clinically asymptomatic concentrations of sarin can cause relatively long-term memory impairments in sarin-poisoned rats when the rats are exposed to clinically asymptomatic sarin concentration repeatedly.

Administration, Inhalation↗
PubMed2001

Toxic effects of sarin in rats at three months following single or repeated low-level inhalation exposure.

Male albino Wistar rats were once or repeatedly exposed to three various low concentrations of sarin for 60 min. in the inhalation chamber. The clinical status of control as well as sarin-poisoned rats was tested 3 months after exposure to sarin using biochemical, haematological, neurophysiological, behavioural and immunotoxicological methods. While biochemical and haematological parameters, including the activities of cholinesterases in erythrocytes, plasma and various organs (brain, diaphragm), did not differ from the control values regardless of the sarin concentration used, few signs of sarin-induced neurotoxicity and immunotoxicity in sarin-poisoned rats were demonstrated. This was especially true when the single exposure of rats to non-convulsive symptomatic concentration and repeated exposure of rats to clinically asymptomatic concentration of sarin was used. In rats repeatedly poisoned with clinically asymptomatic concentrations of sarin, the alteration of the gait characterized by ataxia, the increase in the stereotyped behaviour, the increase in the excitability of the central nervous system following the administration of the convulsive drug pentamethylenetetrazol were observed. In rats poisoned with non-convulsive symptomatic concentration of sarin, the subtle supression of spontaneous, as well as lipopolysaccharides-stimulated, proliferation of spleen lymphocytes and the bactericidal activity of peritoneal macrophages was primarily observed besides the signs of neurotoxicity. Our findings confirm that both non-convulsive symptomatic and clinically asymptomatic concentrations of sarin can only cause very few, subtle long-term signs of neurotoxicity and immunotoxicity in sarin-poisoned rats when the rats were exposed to asymptomatic sarin concentrations repeatedly.

Administration, Inhalation↗
PubMed2001

The long-term influence of low-level sarin exposure on behavioral and neurophysiological functions in rats.

1. Long term effects of low doses of highly toxic organophosphorus agent sarin on behavioral and neurophysiological functions were studied in rats exposed to sarin by inhalation. The toxic effects of sarin were monitored using a functional observational battery (FOB), an automatic measurement of motor activity and a test of excitability of central nervous system at 3, 6 and 12 months following sarin exposure. 2. The results indicate that sarin at symptomatic as well as asymptomatic doses (level 2 and 3) is able to induce some neurotoxic effects (a decrease in activity and mobility, an alteration of gait, an increase in stereotyped behavior) including an increase in the excitability of central nervous system (an increase in convulsive activity following the administration of pentamethylenetetrazole) in rats at 3 months following inhalation exposure. Some sings of increased excitability were also observed in sarin-exposed rats following 6 or 12 months (an increase in exploratory activity, body temperature and a hindlimb grip strength at 6 months following exposure to sarin at asymptomatic doses, an increase in tail-pinch response at 12 months following exposure to sarin at symptomatic doses). 3. Therefore, nerve agents such as sarin seem to be harmful not only at high, clinically symptomatic doses but also at low, clinically asymptomatic doses because of long term manifestation of alteration of neurophysiological functions in sarin-exposed rats without disruption of cholinergic nervous system.

Animals↗
PubMed2001

Long-term effects of low-level sarin inhalation exposure on the spatial memory of rats in a T-maze.

1. To study the influence of low-level sarin exposure on cognitive functions, male albino Wistar rats were exposed to three various low concentrations of sarin (LEVEL 1-3) for 60 minutes in the inhalation chamber. Testing of cognitive functions was carried out using the T-maze evaluating learning and spatial memory. The behavior of sarin-exposed rats in the T-maze was tested several times within five weeks following sarin inhalation exposure to look for any cognitive impairments. The alteration of cognition was evaluated by using a method studying memory elicitation in response to appetitive motivation in a multiple T-maze. 2. Statistically significant, short-term deficiency in the T-maze performance was observed in rats exposed to symptomatic (LEVEL 3) as well as clinically asymptomatic concentration (LEVEL 2) of sarin. The repeated exposure of rats to clinically asymptomatic dose of sarin (LEVEL 2R) did not change the effect of low-level sarin exposure on spatial memory compared to the single exposure to the same dose of sarin. 3. Thus, sarin is able to influence the cognitive functions (e.g. spatial memory) even at low doses that do not cause clinically manifested intoxication following the inhalation exposure. Nevetheless, the alteration of spatial memory lasts for a short time only, in contrast with the severe sarin poisoning.

Administration, Inhalation↗
PubMed2000

Neuroprotective effects of currently used antidotes in soman-poisoned rats.

The neuroprotective effects of antidotes (atropine, obidoxime, obidoxime/atropine mixture) on rats poisoned with soman at a sublethal dose (54 microg/kg, im, 80% of LD(50) value) were studied. The soman-induced neurotoxicity was monitored using a functional observational battery (FOB) and an automatic measurement of motor activity. The neurotoxicity of soman was monitored at 24 h and 7 days following soman challenge. The results indicate that obidoxime alone is not able to protect the rats from the lethal effects of soman. Three soman-poisoned rats treated with obidoxime alone died within 24 h. On the other hand, atropine alone or combined with obidoxime allows all soman-poisoned rats to survive within 7 days following soman challenge. Atropine alone and combined with obidoxime seems to be relatively effective antidotal treatment for the elimination of soman-induced neurotoxicity in the case of sublethal poisonings, although the antidotal mixture is significantly less effective than atropine alone because obidoxime can counteract the beneficial effects of atropine. Obidoxime appears to be practically ineffective to diminish soman-induced neurotoxicity. The neuroprotective effects of antidotal mixture consisting of atropine and obidoxime depend on the antimuscarinic effects of atropine only. Thus, the replacement of obidoxime by more effective acetylcholinesterase (AChE) reactivators is necessary to increase the neuroprotective efficacy of antidotal treatment in the case of soman poisonings.

Animals↗
PubMed1999

Influencing of spatial memory in rats by DSP-4 and mescaline.

Behavioural effects of two experimental neurotoxins, mescaline and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), on retention of spatial orientation were studied in the T-maze. The stereotaxic administration of both neurotoxins into the selected brain structures was chosen to reveal this effect. The intensity and time course of the neurotoxic effect were dependent on the brain area administered. Nevertheless, the lengthening of the latencies in reaching the goal was generally more marked after mescaline in comparison with DSP-4.

Animals↗
PubMed1999

Neuroprotective effects of antidotes in soman-poisoned rats.

1. The neuroprotective effects of antidotes (atropine, obidoxime/atropine mixture, HI-6/atropine mixture) on rats poisoned with soman at a sublethal dose (48 micrograms/kg i.m.; 60% of LD50 value) were studied. The neurotoxicity was monitored using a functional observational battery (FOB) and an automatic measurement of motor activity. The neurotoxicity of soman was monitored at 24 h and 7 d following soman poisoning. 2. The results indicate that atropine alone and the oxime HI-6 in combination with atropine seem to be effective antidotal treatment for the elimination of soman-induced neurotoxicity in the case of sublethal poisonings. 3. On the other hand, the combination of obidoxime with atropine appears to be practically ineffective in diminishing neurotoxic soman-induced symptoms. 4. Dealing with neuroprotective effects of antidotes, the oxime HI-6 in combination with atropine seems to be more suitable antidotal mixture than obidoxime in combination with atropine even in the case of sublethal poisoning with nerve agents.

Animals↗
PubMed1993

Methods for testing of compounds with non-lethal effect.

The effect of some toxic chemicals differing in their mechanism of action was studied by means of the method of the spontaneous motoric activity. Qualitative and quantitative changes in behaviour following administration of sublethal doses of these compounds were found. Depending on the doses administered, exploratory activity (both horizontal and vertical) following soman administration was decreased. Very low doses of VX decreased motoric activity of animals in dependence in time of its action. Anticholinergic substance QB significantly increased the frequency of motor activity. Noradrenergic neurotoxin DSP 4 decreased both horizontal and vertical activities depending on time of its exposition. The increase followed by decrease of spontaneous motor activity was observed following administration of yperite.

Animals↗
PubMed1989

Effects of mescaline and its derivative N-[3,4,5-trimethoxyphenylethyl]-aziridine on the spatial orientation of rats in a T-maze.

The central effect of mescaline and of its derivative N-[3,4,5- trimethoxyphenylethyl]-aziridine (FAZ) after their stereotaxic administration into the lateral ventricle of the brain was studied in behavioural experiments on rats. The effect of the two substances was tested by a method studying memory elicitation in response to appetitive motivation in a multiple T-maze. The results show that both substances worsened the behaviour in question. The negative effect of mescaline (lengthening of the time of passage through the maze) was manifested both immediately and several weeks after a single dose. FAZ likewise worsened the test reaction, but its effect was less pronounced than that of mescaline.

Animals↗