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Biomedical subjects

L S Godlevskiĭ

Publications and source records attributed to L S Godlevskiĭ.

At least 37 records · Page 2Linked to original sources

[The role of the substantia nigra in the anticonvulsive and antiaggressive effects of diazepam during pharmacological kindling].

The seizure activity was investigated on the model of pharmacological kindling which was induced by repeated picrotoxin injections in the subthreshold dose, after the tryptic fragment of T5 protein-human diazepam binding inhibitor (DBI) (10 micrograms) injection into a reticular part of substantia nigra. An increase in the seizure reaction and suppression of the antiseizure diazepam action were observed. Intranigral DBI injection induced no change in a threshold of "attacks" in rats which were induced through electric shocks delivered to animals with an electrode floor and no changes in antiaggressive diazepam action were observed under such conditions.

Aggression↗

[Effects of extracts of different parts of the brain of kindled animals on seizure activity of recipient rats].

The peptide-containing fraction was emitted from the hippocampal and ventral mesencephalic region tissue of rats kindled with subconvulsant doses of corazol. Extracts were prepared by the help of hot acetic acid on the stage of generalized clonic-tonic seizure development. The intraventricular injection of VMR-extracts in relatively high dose increased seizure reactions which were induced in intact recipient rats by intraperitoneal corazol injection. The intraventricular injection of the extract in relatively low dose (100 times less) suppressed corazol-induced seizures in recipients. Data are discussed from the point of view of pathological epileptic system formation and the role played by peptides in supporting it's activity during pharmacological kindling.

Animals↗

[Modeling of torsion dystonia through electric stimulation of the vermis cerebellum cortex].

It was shown in acute experiments on cats that electrical stimulation (ES) (100-300 Hz, 5.0-10.0 V) of cat's cerebellar vermal cortex (lobules V and VI) was followed by head deviation in the direction opposite to that side on which the animal was laying, posture and movement disturbances and also by simultaneously occurred contraction of musculus-antagonists of extremities. The tonic and posture disturbances were observed during 40-60 s after ES cessation. During this time in the zone of ES in cerebellar cortex the high-amplitude synchronized activity was registered which was due to generator of pathologically enhanced excitation (GPEE) formation. Intraperitoneal diazepam (0.5-1.0 mg/kg, 30 min before the observation) pretreatment suppressed GPEE formation that correlated with suppression of syndrome manifestations. The conclusion was made that cerebellar hyperactive cortex, which was due to GPEE induction, might have played the role of pathological hyperactive determinant structure of the described syndrome.

Animals↗

[Appearance of parkinsonian syndrome after administration of delta sleep-inducing peptide into the rat substantia nigra].

Bilateral microinjection of delta-sleep-inducing peptide (DSIP) (10.0 nmol) into the substantia nigra provoked hypokinesia and rigidity in rats observed during 4.0 hours. Injection of DSIP in dose of 5.0 nmol into the substantia nigra or into the nuclei caudati in dose of 10.0 nmol did not induce such symptoms. The enhanced slow-wave activity was recorded in caudate nuclei during hypokinesia and rigidity which demonstrated the formation of the generator of pathologically enhanced excitation (GPEE). The systemically cyclodol administration resulted in abolishment of rigidity and increase in locomotor activity. The conclusion is that bilateral intranigral DSIP injection caused acute parkinson syndrome in rats due to the formation of cholinergic GPEE in caudate nuclei. The hyperactive caudate nuclei act as the pathologic determinant which induces the parkinson syndrome.

Acute Disease↗

[Effects of destruction and activation of limbic structures on formation of convulsive and emotional disorders during picrotoxin kindling].

In the experiments on rats it was shown that the picrotoxin kindling, which consists of the progressive increasing of convulsive reactions during daily systemic administration of picrotoxin in subconvulsive dosages results also in the development of the pathologically enhanced defensive reactions. The destruction of hippocampal structures by kainic acid prevented the seizure syndrome, while their activation due to blood injection in hippocampus promoted its development; under these conditions the kindling of pathologically enhanced defensive reactions was not significantly changed. Bilateral amygdalar destruction significantly attenuated the development of pathologically increased defensive behavior; under these conditions the seizure syndrome was not significantly changed. The data are discussed on the theory of generator, and systemic mechanisms of neuropathologic syndromes and show that picrotoxin kindling results in the formation of two different pathologic systems which cause the development of two mentioned syndromes: seizure syndrome and syndrome of pathologically enhanced defensive behavior.

Amygdala↗

[Effect of delta sleep-inducing peptide, anticonvulsant preparations and nicotinamide on generalized seizure activity].

The influence of delta-sleep inducing peptide (DSIP) upon seizures induced by corazol, bicuculline, picrotoxin, strychnine, thiosemicarbazide were investigated in experiments on F1(CBA X C57 BL/6) mice. It was shown that DSIP increased the latency of first seizure manifestation which were induced by corazol, bicuculline and picrotoxin and also resulted in a suppression of seizure severity of corazol and bicuculline induced seizures. Anticonvulsant action of DSIP was evident under the condition of the mild severity seizures development. The effect of DSIP was mostly pronounced in range of its doses from 10 to 100 mcg/kg. DSIP when combined with phenobarbital, carbamazepine, diphenylhydantoin or nicotinamide enhanced the antiepileptic effects of these anticonvulsant drugs.

Animals↗

[Effect of brain extracts from rats subjected to korazol kindling on generalized epileptic activity].

The pharmacological kindling was induced in rats by corazol repeated injections in subthreshold doses. The peptide-containing fraction was emitted from animal brains by the help of hot acetic acid on the stage of generalized clonic-tonic seizures development. Intraperitoneal injection of brain extracts of kindled rats significantly increased corazol and picrotoxin induced seizure severity in mice. The effect was removed by preliminary injection of naloxone or by preventive incubation of extracts with pronase. Intraventricular injection of extracts to intact rats increased the seizure severity which was provoked by corazol and in high doses induced in rats generalized seizure reactions.

Animals↗

[Development of motor and emotional disorders in rats during daily administration of subliminal doses of picrotoxin].

It was shown in the experiments on rats, that three neuropathological syndromes develop as a result of daily subthreshold picrotoxin injections (1.25 mg/kg). Maximal expression of syndromes was different during various periods of kindling. The development of seizure syndrome was followed by prevalence of enhanced electrical activity in hippocampus; the development of "akinetic" syndrome was the same in the caudate nuclei. Data are discussed on the positions of theory of the generator, determinant and systemic mechanisms of neuropathological syndromes.

Animals↗

[Anticonvulsant properties of the cerebrospinal fluid during activation of the antiepileptic system of the brain].

Cerebrospinal fluid (CSF) was obtained after 30-40 sessions of daily electrical stimulation of the cat cerebellum vermis. The intraventricular injection of CSF (10 microliters) to Wistar rats increased the latent period of initial seizure manifestations, significantly reduced the number of animals with seizures and reduced the severity of seizures induced by korazol injection (40 mg/kg). Analogous seizure changes were observed in rats after intraventricular injection of CSF (10 microliters) from cats subject to 3-10 electroshock seizure fits. Intraventricular injection of CSF (250 microliters) obtained from cats after electroshock to cats with strychnine-induced epileptic foci in the brain cortex led to the suppression of the epileptic activity. The conclusion was made that different ways of antiepileptic system activation cause the accumulation of endogenous antiepileptic substances in CSF.

Animals↗

[The effect of delta sleep-inducing peptide on the convulsive activity in corasol kindling].

The influence of intraperitoneal delta-sleep inducing peptide (DSIP) injection (100 micrograms/kg) on the epileptic activity was investigated in the experiments on Wistar rats and (CBA X C57B1/6)F1 mice. The model of chronically developing epileptic activity--the model of pharmacological kindling--was created by daily repeated corasole injections in subconvulsive doses (30 mg/kg). It has been shown that DSIP injection delayed the manifestation of generalized seizures during kindling, led to the suppression of seizure activity and reduced the mortality rate of animals that developed kindled seizures. The antiepileptic effect of DSIP was observed throughout the period of 5 minutes to 24 hours after the injection. Naloxone (2.5 mg/kg) did not change the antiepileptic effect of DSIP.

Animals↗

[Modelling of the parkinsonian syndrome by the administration of kainic acid into the caudate nucleus].

The experiments on rats have shown that bilateral administration of kainic acid (0.1-0.15 microgram) into the rostral parts of caudate nuclei led to the development of hypokinesia and rigidity. An increase in the electrical activity--the formation of the generator of pathologically increased excitement (GPIE) was noted in a zone of kainic acid injection. Rigidity and hypokinesia were attenuated and the GPIE activity was depressed after cyclodol (1-10 mg/kg) or L-DOPA (100-200 mg/kg) administration. Combined administration of cyclodol (2 mg/kg) and L-DOPA (50 mg/kg) induced potentiated antiparkinsonian effect. Dopamine microinjections into the GPIE area depressed its activity and abolished rigidity and hypokinesia. These data suggest that the Parkinson syndrome develops under the influence of GPIE induced by kainic acid administration into caudate nuclei.

Animals↗

[Effect of the delta sleep peptide on epileptic activity in the cerebral cortex of rats and cats].

In free behaviour experiments on rats it has been shown that the intraperitoneal injection of delta sleep-inducing peptide (DSIP) (100 micrograms/kg) suppressed penicillin-induced relatively moderate epileptic foci which generated spike potentials as well as severe foci with ictal epileptic discharges. In the experiments on cats it was shown that intravenous DSIP injection (100 micrograms/kg) suppressed strychnine-induced epileptic focus and complexes of epileptic foci.

Animals↗

[Changes of the dehydrogenase activity in the hippocampus in the korazol-induced kindling phenomenon].

The activity of glutamate, succinate, malate and lactate dehydrogenases in neuronal and glial hippocampal cells during corazol kindling has been cytophotometrically assessed in the experiments on (CBA X C57BL/6)F1 mice. The kindling was induced by regular intraperitoneal corazol injections in subliminal dose of 30 mg/kg. Histochemical investigations were performed 30 min, 24 hours and 30 days after the corazol injections were discontinued. The changes in the enzymatic activity revealed suggest the biphasic nature of the disturbances in energy metabolism. During the first phase (24 hours after the last injection) the enzymatic changes do not have a noticeable influence on the predominant aerobic type of oxidation. In the second phase (30 days after the last injection) lactate dehydrogenase activity significantly increases, while the activity of other enzymes under study reduces.

Animals↗

[Changes in the dehydrogenase and GABA transaminase activity in the cerebral cortex during corazol kindling].

The experiments on (CBA X C57BL/6)F1 mice have shown that regular corazol injections in subliminal doses stimulated seizure susceptibility (pharmacological kindling). Cytophotometric assay of the activity of oxidative metabolism enzymes (glutamate dehydrogenase, malate dehydrogenase, succinate dehydrogenase, alpha-oxoglutarate dehydrogenase, lactate dehydrogenase) and GABA-transaminase in the sensorimotor cortex of kindled mice in post-convulsive period, and 24 hours or 30 days after corazol injections were discontinued, has revealed some specific alterations of the enzymes under study, that suggest the existence of two phases of energy metabolism disturbances. The first phase (24 hours after corazol injections were discontinued) is characterized by intensified succinic acid oxidation, while the second phase (30 days after the last injection) is characterized by anaerobic glycolysis in neuronal and glial cells. Inhibition of GABA-transaminase activity was particularly marked in postconvulsive period. From a molecular point of view these data may be considered as enzyme disturbances during stimulation of seizure susceptability or seizure activity and as a compensation component ensuring anticonvulsive mechanisms and reparative processes (antagonistic principle of molecular mechanism regulation) during activation of antiepileptic system.

4-Aminobutyrate Transaminase↗

[The hippocampus as the determinant structure generating epileptic activity during korazol kindling].

It has been shown in chronic experiments on rats that two periods of EEG and behavioral alterations may be distinguished during korazol kindling. The bursts of slow waves and spike-wave activity appear on the EEG during the first period as response to subthreshold doses of korazol, which is accompanied behaviorally by standing and myoclonuses. The second period is characterized by the appearance of high-frequency polymorphous generalized seizure discharges on the EEG accompanied by clonicotonic seizures. Interictal and ictal epileptic discharges appear primarily in the hippocamp and then in other brain structures during the development of korazol kindling. The conclusion is made that the hippocamp plays the role of a pathological determinant structure in the development of chronic brain epileptization during korazol kindling.

Animals↗

[Effect of destruction of the hippocampus and caudate nucleus on the development of epileptic activity during corazole kindling].

Experiments were carried out on random-bred white rats (250-350 g). Kindling was induced by daily intraperitoneal corazol injections in subthreshold (subconvulsive) doses (30 mg/kg). It has been demonstrated that bilateral hippocampal destruction did not change the seizure threshold, while bilateral caudate nucleus destruction lowered it. Hippocampal destruction delayed corazol kindling development and also accelerated the lowering of seizure susceptibility after corazol injections were discontinued, as compared to control animals. Caudate nucleus destruction induced more marked seizure reactions in the first 14 days after corazol injections were started. There were no significant differences in seizure manifestation severity in kindled and control groups. These data point to an essential role of caudate nucleus as an element of antiepileptic system and support the concept that hippocampus plays a role of pathologic determinant which is associated with the formation of an epileptic system underlying corazol kindling.

Animals↗

[Effect of vitamin preparations on epileptic activity].

It has been shown in experiments on mice and rats that daily administration of subthreshold doses of pentylenetetrazol led to a progressive increase in the sensitivity to the action of the epileptogen, augmentation of brain epileptization and development of the pharmacological kindling. Single administration of nicotinamide in doses of 250, 500 and 1000 mg/kg and alpha-tocopherol in a dose of 100 mg/kg exerted a pronounced antiepileptic effect under the conditions of over kindling. On combined use of nicotinamide and pyridoxal-5-phosphate, nicotinamide, pyridoxal-5-phosphate and alpha-tocopherol the antiepileptic action was more demonstrable. Daily administration of a complex of the drugs (nicotinamide, pyridoxal-5-phosphate, alpha-tocopherol) produced a substantial reduction in epileptic activity under the conditions of overt kindling. The possibility has been demonstrated of preventing the development of epileptic activity with nicotinamide under kindling.

Animals↗

[Cytophotometric study of changes in glutamate dehydrogenase and GABA transaminase in the cerebral cortex during corazole kindling].

It has been demonstrated in (CBA X C57BL/6) F1 mice that daily corazole injections (30 mg/kg) lead to the development of pharmacological kindling that manifests in a progressive increase of seizure susceptibility, seizure occurrence in response to the subthreshold convulsant dose and in demonstrable seizures. Cytophotometric study of the histological specimens of the sensorimotor cortex discovered the reduced enzymatic activity of glutamate dehydrogenase and GABA transaminase in the neurons. In the neuroglial cells, the activity of glutamate dehydrogenase also declined, whereas that of GABA transaminase tended on the contrary, towards increase.

4-Aminobutyrate Transaminase↗