PubMed Health⌕ Search

Biomedical subjects

S Gralewicz

Publications and source records attributed to S Gralewicz.

At least 37 records · Page 2Linked to original sources

Development of spontaneous, age-related nonconvulsive seizure electrocortical activity and radial-maze learning after exposure to m-xylene in rats.

It has been hypothesized that exposure to neurotoxins may result in accelerated ageing of the central nervous system (CNS). The present study investigated the effects of a 3-month (6 hr daily, 5 days/week) inhalation exposure of rats to m-xylene, at concentrations of 100 and 1000 ppm, on the spontaneous neocortical spike and wave discharges (SWD) and spatial learning in an eight-arm radial maze. According to the literature, the SWD activity increases and the ability to solve spatial problems worsens as the animal gets older. The testing in the maze (one trial daily for five days) was performed two months after the exposure. The SWD activity was assessed on the basis of the number and duration of SWD bursts in one-hour EEG recordings performed before the exposure, on day 28, 56 and 84 of exposure, and then on day 14, 28, 42, and 84 after the exposure. In rats exposed to 1000 ppm m-xylene, unlike in the controls, neither decrease in the number of omission errors nor decrease in response speed was noted in the course of training in the radial maze, which suggested a learning deficit. However, the development of the age-related SWD activity was significantly retarded in these rats when compared with the controls. In rats exposed to 100 ppm m-xylene, the effects on maze behaviour and the SWD activity were similar as in rats exposed to 1000 ppm m-xylene but they were less pronounced. The study has provided an experimental evidence for persistent changes in the CNS functions, resulting from a subchronic exposure to m-xylene. The changes, however, cannot be interpreted simply as an accelerated brain ageing.

Administration, Inhalation↗

Changes in cortical and hippocampal EEG activity accompanying spontaneous electrocortical seizures in rats.

The purpose of the present study was to find out whether the occurrence of bursts of spontaneous spike-wave discharges (SWD) in rat neocortex is related to a particular state of vigilance (level of arousal), as some authors suggested, or rather to transitions from one state to another as postulated by others. Patterns of cortical and hippocampal EEG preceding and following the SWD bursts were studied in rats. It has been found that the beginning of an SWD episode is usually preceded by a shift of cortical activity toward synchronization and replacement of the rhythmic slow activity (RSA) in the hippocampus by large irregular activity (LIA). After SWD, the cortical activity is usually more desynchronized and RSA is present more frequently than just before its onset. An analysis of selected episode-free and episode-rich EEG segments revealed that SWD's occur in abundance at the periods characterized by frequent changes of the hippocampal EEG pattern but are absent during the periods in which long-lasting RSA trains dominate in the record. Thus, the data confirm that SWD occurrence is related more to transitions from one state to another than to a particular state as such. They also indicate that the preferable conditions for SWD's appear when arousal is decreasing from a moderate to a lower level.

Animals↗

Spontaneous seizure electrocortical activity in rats: relation to arousal level.

The relationship between neocortical high voltage spindle activity (HVS) and the level of arousal (state of vigilance) was investigated in imp-DAK rats. Two groups of single records (6 h and 24 h) and one group of repeated ones (6 h daily for three consecutive days) were analysed. Five levels of arousal (states) were distinguished on the basis of hippocampal and neocortical EEG: high arousal (HA), moderate arousal (MA), low arousal (LA), slow wave sleep (SWS) and paradoxical sleep (PS). The number of HVS episodes and the cumulative amount (i.e. summed duration) of each state was calculated for each successive hour of recording. It was found that the number of HVS episodes correlated positively with the amount of the MA state, but not with the amount of the remaining states. The rate of HVS occurrence during the MA state, however, was not stable. It decreased along with the decrease in amount of MA in successive recording hours of the same recording session. However, at the beginning of each successive session, the HVS episodes became more numerous, whereas the MA amount decreased. The accompanying changes in the cumulative amount of the remaining states confirm indirectly the supposition that HVS occurrence is related to transitions from one state to another rather than to a given state itself.

Animals↗

[Evaluation of the functional observational battery of tests used for neurotoxicity detection based on the effects of exposure to chlorfenvinphos].

Functional observational battery suggested by EPA, was applied to neurotoxicity screening studies. In previous experiments an organophosphorous pesticide, chlorfenvinphos (CVP), was used. It was administered intraperitoneally to male rats at the doses of 1, 3, 6 mg/kg of body weight; edible oil was administered to the control group. Tests were performed 3 hrs, 24 hrs and 7 days after the administration of the these substances. The set of tests concerned motor, sensory and vegetative functions. The influence of the dose of 6 mg/kg on rats was particularly evident. A number of disorders, like tremor, hypersalivation, dysbasia and hypotaxia, not observed in animals to which lower doses of CVP had been administered, were noticed. The mortality rate in this group was 25%. Earlier studies revealed neurotoxicity of CVP administered at the dose of 3 mg/kg, which when compared to the present results of the experiment indicates low sensitivity of this battery of tests taken as a whole. The disadvantage of the battery lies also in applying the quality evaluation scale in many cases, which makes carrying out statistical analysis difficult. Behaviours not formulated in this scale were observed. The observation of animal locomotor activity proved to be the most reliable and objective neurotoxicity evaluation index both in the previous and present studies.

Animals↗

Hippocampal rhythmic slow activity (RSA) in the cat after intraseptal injections of muscarinic cholinolytics.

Influence of intraseptal injections of cholinolytics on hippocampal rhythmic slow activity (RSA) was investigated in cats. Results of the first experiment have shown that neither atropine (At) nor scopolamine (Sc) injected into the medial septum in doses of 20 micrograms prevented the induction of RSA by a cholinergic (carbachol-CCh) stimulation of the anterior hypothalamus as well as by electrical stimulation of posterior hypothalamus or periaqueductal grey substance (PAG), and were only partially effective in prevention of the spontaneous RSA. RSA did not appear spontaneously and could not be induced by electrical brain stimulation after intraperitoneal injections of At (2.0 mg/kg) or Sc (0.2 mg/kg). Results of the second experiment have shown that intraseptal injections of At (5.0 or 10.0 micrograms) are also ineffective in prevention of RSA induction by CCh (2.5 micrograms) injected into the same septal locus. The data suggest that the medial septum cannot be regarded as the common muscarinic link within the RSA generating system of the cat.

Animals↗

Tolerance to chlorphenvinphos in rats assessed on the basis of changes in locomotor behavior in rotating wheels.

Spontaneous locomotor activity in rotating wheels was investigated in rats exposed repeatedly (i.p. daily injections, five days a week for two weeks) to an agricultural organophosphorus pesticide, chlorphenvinphos (CVP) at doses of 1.0 and 3.0 mg/kg. After a seven day interval each rat was injected with a single 3.0 mg/kg test dose of CVP in order to assess the stability of tolerance. Concomitant changes in blood and the brain ChE activity were also investigated. It was found that exposure to CVP at a low dose (1.0 mg/kg), resulting in less than 50% reduction of ChE activity in blood and in the brain, did not produce changes in spontaneous locomotion in rotating wheels in the rat. Higher doses (3.0 mg/kg) inhibited blood and the brain ChE by more than 50% and reduced locomotion. Under conditions of repeated exposure to CVP at the symptomatic (3.0 mg/kg) dose ChE activity remained low throughout the exposure period, however, locomotor activity returned to a normal level, i.e. tolerance developed, within less than five days. Seven days after termination of the repeated exposure, the behavioral subsensitivity to CVP still remained. The biochemical data suggest that it may be related, at least partially, to a diminished vulnerability of ChE in some parts of the brain to CVP induced inhibition.

Animals↗

A comparison of changes in spontaneous (EEG) and evoked brain activity induced by chlorphenvinphos and physostigmine in rats and rabbits.

The effects of single i.p. injections of two cholinesterase inhibitors, chlorphenvinphos (CVP) and physostigmine, on hippocampal and cortical EEG and flash evoked potentials in occipital cortex were compared in rabbits and rats. A comprised method of spectral analysis was employed for evaluation of changes in EEG. The obtained results showed that in both species the changes in hippocampal and cortical EEG after administration of CVP were relatively small or negligible in comparison with those after physostigmine administered in doses resulting in comparable (or even lesser) inhibition of blood cholinesterase (ChE). Neither CVP nor physostigmine resulted in significant changes in the morphology of the flash evoked potentials. The data do not confirm the suggestion that brain electrical activity is the most sensitive index of neurotoxicity resulting from exposure to organophosphate ChE inhibitors.

Animals↗

Changes in brain bioelectrical activity (EEG) after repetitive exposure to an organo-phosphate anticholinesterase. II. Rat.

Effects of repetitive exposure (ten times in a period of two weeks) to chlorphenvinphos (CVP), at daily doses of 0.5 and 1.0 mg/kg, i.p., were studied in adult male Wistar rats of imp-DaK stock. It was found that 3 hrs after the last exposure, the cholinesterase (ChE) activity in the blood and brain was close to 50% of the control value in the 0.5 mg/kg group and less than 50% in the 1.0 mg/kg group. In both groups, normalization of ChE activity in plasma took less time than in erythrocytes, and the normalization of ChE activity in erythrocytes proceeded faster than in the majority of the brain areas studied. Electrophysiological investigations revealed a retardation of age-related epileptic-like cortical activity. This effect, however, was present only in the 1.0 mg/kg group, and only in the period of decreased ChE activity in the brain. Spectral analysis revealed an increase in 1-4 Hz activity in the cortical EEG of the 0.5 mg/kg group and heightened theta activity (4-7 and 7-9 Hz bands) in the hippocampal EEG of the 1.0 mg/kg group. The later effects were detected after a time sufficient for full normalization of ChE activity and manifested themselves most clearly in the presence of an acoustic stimulus associated with pain. The above results are in agreement with earlier observations on rabbits exposed repetitively to CVP. Data from both species suggest that, in the case of repetitive exposure to CVP, neither plasma nor erythrocyte ChE activity is a reliable indicator of toxicity, and that such exposure to this OP may lead to changes in EEG outlasting the period of lowered ChE activity in the blood and brain.

Animals↗

Effects of a single exposure to chlorphenvinphos, an organophosphate insecticide, on hot-plate behaviour in rats.

Effect of a single i.p. exposure to an organophosphate insecticide, chlorphenvinphos (CVP), in doses of 1.0 and 3.0 mg/kg (one third and one tenth LD50, respectively), on the latency of the paw-lick response (hot plate test) was investigated in rats before and after a short inescapable footshock. The test was repeated twice on the 18th and 19th days after the exposure, i.e. after a time sufficient for a full recovery of cholinesterase activity in the blood and brain. On the first day of testing the groups did not differ with respect to the paw-lick latency before footshock. However, the paw-lick latency after footshock (the index of stress-induced analgesia) was significantly longer in rats exposed to the higher dose of CVP (3.0 mg/kg) than in the control animals. Twenty four hours later, in the control animals, the paw-lick latencies before footshock were shortened in comparison with those recorded on the day before. An opposite effect was observed in the rats exposed to 3.0 mg/kg of CVP. The data suggest that some alterations in the brain functional state may outlast the CVP induced depression of cholinesterase activity.

Animals↗

Brain electrical activity (EEG) after repetitive exposure to chlorphenvinphos an organophosphate anticholinesterase: I. Rabbit.

Cholinesterase (ChE) activity in blood and brain as well as the hippocampal and cortical EEG were investigated in rabbits exposed once a day for a period of two weeks to an organophosphate insecticide, chlorphenvinphos (CVP). The daily dose of CVP was 14.0 mg/kg i.p. ChE activity in plasma and erythrocytes decreased by 60 and 48%, respectively, by the end of exposure and returned to the preexposure level within 35 days. In the exposed animals, killed and dissected a day after, the ChE activity in blood had been found normal, the level of ChE activity in some parts of the brain was still significantly depressed. The spontaneous hippocampal EEG showed no changes as soon as 24 hours after the exposure. However, after a period sufficiently long for the normalization of ChE activity in blood, the hippocampal arousal response (theta rhythm) to click and to a tone associated with pain was found heightened in the exposed rabbits. Moreover, spectral analysis of 5 minute EEG samples revealed a decrease in the content of 7-13 Hz activity in the cortex of the exposed animals as compared to the control ones. The obtained data suggest that exposure to CVP may lead to functional changes in the brain outlasting the period of ChE depression.

Animals↗

Changes in physiological and electrophysiological parameters in rabbits after single exposure to chlorphenvinphos.

In order to evaluate some of the central effects of an organophosphorus pesticide--chlorphenvinphos (CVP), the time course of changes in the activity of blood cholinesterase (ChE), body temperature and hippocampal EEG were compared in rabbits after acute i.p. exposure. The pesticide was administered twice at an interval of 80-90 days. The Deichmann-LeBlanc scheme of dosing (one animal/one dose) was adopted starting with 22 mg/kg. CVP resulted in a dose-dependent decrease in plasma and erythrocyte ChE activity, a decrease in body temperature ranging from 0.7 degrees to 3.5 degrees C, and in an increase in content of the immobility-related, rhythmic slow activity (I-RSA) in the hippocampal EEG. Changes in body temperature appeared at lower doses than those in the hippocampal EEG. Contrary to the changes in ChE activity, which lasted 4-30 days, those in body temperature and in hippocampal EEG disappeared within 24 hours after the injection. CVP administered at the same dose 80-90 days after the first injection, resulted again in an inhibition of ChE activity, but the effect on the hippocampal EEG was less clear, and that on body temperature was variable; no effect, an increase or a decrease appeared. The data suggest that: i) body temperature is a more sensitive index of a central action of CVP administered for the first time than the hippocampal EEG; ii) the brain cholinergic mechanisms are relatively resistant to the acute action of the OP and undergo fast adaptive changes; iii) even single exposure to CVP may produce some long-lasting functional changes in the brain of some subjects, which has been proven by the changed response to the second exposure.

Animals↗

Neurotoxicity of chlorphenvinphos an organophosphorus pesticide: effects on blood and brain cholinesterase activity, open field behavior and response-to-change in a "T" maze in rats.

Cholinesterase (ChE) activity in blood (plasma and erythrocytes) and in different parts of the brain, open field behavior and response-to-change in a "T" maze were investigated in separate groups of rats after a single intraperitoneal exposure to an organophosphorus pesticide - chlorphenvinphos. The doses used were 3.0 mg/kg or 1.0 mg/kg which amounted to approximately, 1/3 and 1/10 of LD50 for this species. The exposure resulted in a dose dependent inhibition of ChE in blood, as well as in the brain. No marked differences in the level of ChE inhibition in plasma, erythrocytes, and in selected parts of the brain (cerebellum, brain stem, diencephalon, hippocampus and the anterior part of the hemisphere) were noted after a given dose. In general, 3 hours after the exposure, ChE was inhibited by about 80% in the case of the 3.0 mg/kg dose and by no more than 50% in the case of the 1.0 mg/kg dose. In blood as well as in the brain, the normalization of ChE activity proceeded at a similar rate, being accomplished within 14 days and within 94 hours after the 3.0 mg/kg and 1.0 mg/kg dose, respectively. No changes suggesting an impairment of short-term memory were observed in the "T" maze until the end of testing (i.e. up to the fourteenth day after the exposure). In the open field, a short-term decrease (up to the third day) in locomotor and exploratory activity was observed only in rats exposed to 3.0 mg/kg of the pesticide. At the end of testing (10-14th day after the exposure) the introduction of a new object into the open field resulted in an increase of locomotor and exploratory activity in control animals but not in the rats exposed to chlorphenvinphos in the 3.0 mg/kg as well as in the 1.0 mg/kg. This suggests that exposure to chlorphenvinphos may result in some behavioral disturbances lasting longer than the ChE recovery.

Animals↗

Effects of single exposure to chlorphenvinphos, an organophosphate insecticide, on electrical activity (EEG) of the rat brain.

The effect of a single exposure to an agricultural insecticide, chlorphenvinphos (CVP), an organophosphorus anticholinesterase, on neocortical seizure activity induced or promoted by cardiazol, and on hippocampal and neocortical EEG was studied in rats. It was found that CVP, given intraperitoneally in doses of 1.0 and 3.0 mg/kg, resulted in no changes in the number and in the duration of epileptic bursts occurring spontaneously, as well as in the content of the hippocampal theta rhythm. The effect of cardiazol (12.5 mg/kg, i.p.) was slightly diminished when the drug was given 3 hours, but not 14 days, after the injection of CVP. I.p. injection of a carbamate cholinesterase inhibitor, physostigmine, in a dose of 1.0 mg/kg resulted in a dramatic increase of the theta content in the hippocampal EEG, and in the total disappearance of the spontaneous seizures. Determination of cholinesterase activity in blood and in the brain in a separate group of subjects showed that after injection of physostigmine (1.0 mg/kg), the inhibition of this enzyme does not exceed the inhibition after injecting CVP in the doses used. It has been suggested that the differences between CVP and physostigmine in their potential to reduce spontaneous epileptic activity and to induce the hippocampal theta rhythm may be due to somewhat antagonistic action of CVP on cholinergic postsynaptic receptors.

Animals↗

Changes in hippocampal and cortical EEG after intraventricular administration of cholinolytics in rabbit and cat.

Effects of central (intraventricular) and peripheral (intraperitoneal or intravemus) injections of muscarinic cholinolytics: atropine sulphate, atropine nitrate and scopolamine hydrobromide, on hippocampal and neocortical EEG were compared in rabbits and in cats. Both salts of atropine might produce epileptic, electrical activity in the neocortex and in the hippocampus when they were administered intraventricularly in doses of 600 microgramm or more (rabbits) and in doses of 50-100 microgramm (cats). Scopolamine hydrobromide injected via the same route in similar doses was mot effective. The data suggest that the epileptic symptoms evoked by atropine are probably due to an action on a neuronal substrate common to both species used and that the action is mediated not through cholinergic, muscarinic receptors.

Animals↗

The effect of amphetamine on hippocampal EEG and EOG activity in cats.

The effect of anorectic dose of amphetamine on some correlates of arousal (hippocampal EEG and EOG activity) was examined in cats. After injection of amphetamine the frequency of hippocampal rhythmic slow activity and EOG activity increased when preinjection value of rhytmic slow activity was low, but decreased when it was high. Thus, amphetamine anorexia may be accompained with an increase as well as with a decrease of arousal level.

Amphetamine↗

Effects of hippocampal stimulation on retention and extinction of one way active avoidance response in cats.

We found previously that hippocampal stimulation (HiSt) at 20 cps, 100 mikroA, applied jointly with a tone (500 Hz) CS in the course of retention test, improved the performance and retarded the extinction of one way active avoidance response (AAR) in cats. During this test failures to perform the AAR were not punished in all but two trials it the beginning of each session. The first experiment of the present studies demonstrated that - (i) the AAR facilitating the effect of HiSt might be prevented by m all electrolytic lesions made around the tips of the stimulating electrodes, (ii) large lesions of the hippocampus exerted little effect on the AAR acquisition, but the response was extinguished faster during the retention test. In the second experiment two response prevention trials (non-reinforced presentations of the CS with no possibility to make the AAR) were run at the beginning of each session after the end of training. In these conditions the HiSt resulted in a faster extinction of the AAR as compared with implanted unstimulated animals. Large lesions of the hippocampus had no effect on the extinction rate. We conclude that the facilitation of retrieval from memory may be responsible for the effects of HiSt on conditioned behavior.

Animals↗

Facilitatory effects of electrical stimulation of the hippocampus on a one way active avoidance response in cats.

Effects of a low intensity electrical stimulation of the hippocampus (HiSt) on acquisition, performance and retention of a one-way active avoidance response (AAR) were studied in four groups of cats. The animals were first trained in avoiding an electric foot-shock signalled by a CS (500 Hz tone) presentation and then they were tested or retention until the response extinguished. The HiSt was applied simultaneously with the CS presentation and terminated immediately after the performance of the AAR. One group of cats was stimulated during training, one during the retention test, one during training and during the retention test and one served as unstimulated control group. It was found that application of the HiSt during training did not influence the acquisition rate, but the stimulation became indispensable for a normal performance and for retention of the response. Application of the HiSt after training facilitated performance and improved retention, but only in cats unstimulated during training. Additional tests revealed that the facilitatory effects of the HiSt could not be attributed to disinhibitory or cue properties of the HiSt.

Animals↗

Relationship between some behavioral and electroencephalographic changes induced by intrahypothalamic injections of carbachol in the cat.

The relationship between changes in the hippocampal EEG, oculomotor activity and vocalization (growling), produced by intrahypothalamic injections of 10 mikrog of carbachol (CCh), was investigated in cats. The injections of CCh resulted in a continuous hippocampal rhythmic slow activity (RSA) of initially increasing and then decreasing frequency. These changes in RSA frequency were positively correlated with changes in oculomotor activity, but not with those in the intensity of the vocal response - growling. A pretreatment of the hypothalamus with atropine sulphate (At), but not with hexamethonim (Hx), before the injection of CCh, eliminated the vocal response. Neither the intrahypothalamically given At, nor Rx prevented the appearance of the continuous RSA and the increased oculomotor activity. However, the electroencephalographic and behavioral effects of CCh did not appear after the pretreatment of the hypothalamus with a mixture of At + Hx, or after an intraperitoneal injection of At in a dose of 2.0 mg/kg. The data suggest that (i) the vocal response is a product of an activation of muscarinic, cholinergic receptors in the hypothalamus, (ii) the continuous RSA and the increased oculomotor activity are due to a joint activition of muscarinic and nicotinic cholinergic systems, and (iii) there must be a common muscarinic link mediating the CCh induced changes in the hippocampal EEG.

Action Potentials↗