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Biomedical subjects

R F Makul'kin

Publications and source records attributed to R F Makul'kin.

At least 19 recordsLinked 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↗

[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↗

[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↗

[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↗

[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↗

[Changes in the spectrum of LDH isoenzymes in foci of epileptic activity induced by penicillin in the cerebral cortex of rats].

The correlation between electrophysiological changes and isozymes of LDH of the rat brain cortex was studied in seizure foci induced by application of sodium penicillin. It was discovered that activity of LDH1 was suppressed, and that of LDH5 fraction was elevated in the determinant focus, which indicates the enhanced glucose anaerobic transformation. The spectrum of LDH isozymes did not practically differ from the indicators in control animals in a homotopic region of the contralateral hemisphere prior to creation of the mirror focus. The anaerobic processes were found to be increased in the mirror focus and in the determinant one as well. Similar pattern of changes in electrophysiological and neurochemical characteristics in the determinant and dependent mirror foci attests to the formation of a pathological system out of the two epileptic foci.

Animals↗

[Effect of electric stimulation of the dentate nucleus of the cerebellum on epileptogenic foci in the cerebral cortex].

It has been shown in acute experiments on cats that electrical stimulation (ES, 100-300 Hz) of the dentate nucleus leads to suppression of interictal discharges elicited by application of low concentrated penicillin solution to the neocortex. ES of the nucleus causes activation of discharges in a more powerful focus of seizures. As its activity gradually attenuates the seizure discharges are suppressed during ES. The period of focus existence is shortened by ES of the nucleus. ES of the ipsilateral nucleus produces no marked effect, leading only to the decreased frequency of seizure discharges. It is concluded that the dentate nucleus plays a significant role as part of the brain antiepileptic system.

Animals↗

[Effect of determinant on formation of the complexes of hyperactivity foci in rabbit cerebral cortex].

With the use of weak strychnine solutions foci of enhanced excitability working in independent modes were created in the brain cortex of rabbits during acute experiments. The hyperactive excitability focus induced by concentrated solutions of strychnine played the role of a determinant structure. It enhanced the activity of other foci, united them into a single functional complex and determined the activity pattern of the entire complex. This complex of foci could be destroyed by depression of the determinant focus activity. Disconnection of any other (dependent) focus failed to destroy the complex. The results derived during the research on the new model confirm the general concept of the role played by the determinant structures in the activity of the central nervous system.

Action Potentials↗

[Effect of stimulation of the paleocerebellar cortex on the multifocal cortical epileptogenic complex].

Effects of paleocortex electrical stimulation on multifocal epileptic complex of the brain cortex alone and in combination with benzodiazepines (diazepam, phenazepam) were investigated in experiments on cats. The animals developed complex reactions which included the increased frequency of seizure potentials during stimulation, their suppression after the cessation of stimulation and the postsuppression rise of frequency (dyssuppression). This points to the dualistic character of cerebellar effects on the brain cortex. On being administered before stimulation benzo-diazepines significantly changed the above effects: activation and dyssuppression first disappeared, whereas the suppression of the epileptic activity in the brain cortex remained unchanged.

Animals↗

[Effect of nicotinamide on epileptic activity in the cerebral cortex].

The experiments on cats showed that intravenous administration of nicotinamide suppresses the epileptic activity in a solitary epileptic focus as well as in the complex of epileptic foci produced by strychnine application to various cortical zones under the influence of the most powerful focus that plays the role of a determinant. After the intravenous injection of nicotinamide (50-70 mg/kg) the complex was destabilized and broken down. The epileptic activity in the dependent foci of the complex disappeared first in the more remote from the determinant focus and then in the nearer one. The determinant focus was the last to disappear. The inhibitory effect of nicotinamide is associated with antiepileptic activity. Nicotinamide is suggested to be one of the endogenous drugs which may suppress brain hyperactivity and activate the antiepileptogenic system.

Animals↗

[Effect of electric stimulation of the caudal reticular nucleus of the pons on foci of epileptic activity in the cerebral cortex].

It was shown in experiments on cats that electrostimulation (ES) of the nucleus caudalis reticularis pontis under the destruction of the central grey matter suppressed discharges in a single epileptic focus, created with application of strychnine to the brain cortex and did not suppress the epileptic activity in the complex of foci, formed under the influence of a determinant focus after local application of strychnine to different zones of the neocortex. After increasing the number of foci in the complex the resistance of the latter to suppressive effects of ES of the nucleus caudalis increases too. The complex reduction owing to liquidation of its foci (local application of nembutal) facilitates the suppressive effects of ES of the nucleus caudalis. Under prolonged inhibition of the epileptic activity in the focus, the coagulation of the nucleus caudalis leads after its long-term ES to the recovery of the epileptic activity. The evidence obtained is discussed from the standpoint of the properties of the pathological system (epileptic complex) and the role of the "antisystem" in suppression of its activity.

Animals↗

[Formation of determinant structures and functional complexes in the neocortex when the brain is transected at different levels].

A strychnine focus created in the cat neocortex preparations with mediopontine section and encephale isolé, increased activity in other weaker foci, synchronized discharges in them, united them into a functional complex and determined the character of the whole complex activity. Such an hyperactive focus plays an active role of the determinant structure. In cortex isolé and preparations with mesencephalic section of the stem, a more rapid formation of functional complexes occurred under the effect of determinant focus. Complete elimination of the afferent and thalamo-cortical interactions seems to hinder neither the hypersynchronization of cortex neuronal elements, nor the formation of functional complexes, nor the generalization of seizure activity over the cortex.

Animals↗

[Formation of an epileptic complex in the cerebral cortex and effect of diazepam on it with different levels of cerebral transection].

Effect of diazepam on the activity of the epileptic complex consisting of a number of foci created with strychnine applications to the brain cortex under conditions of intact brain and at different levels of it neuronal isolation was studied in acute and chronic experiments on cats. It was shown that in the preparations of cerveau isolé and cortex isolé a more rapid formation of the epileptic complex under the influence of the determinant focus, and marked generalizaiton of convulsant activity could be observed. Diazepam induced a decrease in the amplitude and frequency of convulsive discharges. There was a break in the synchronization of their appearance first in the dependent foci and then in the determinant one. The diazepam effects were seen both in the intact brain and in the preparations of cerveau isolé and cortex isolé. These findings indicate that diazepam may exert an indirect action on the brain cortex that does not exclude the participation of other brain structures in the realization of the diazepam effect under conditions of intact brain.

Acute Disease↗

[Modeling of determinant and dependent foci of epileptic activity in the rat cerebral cortex].

Foci of increased excitability were created in acute experiments on rats by means of weak strychnine solutions working at independent regimens. The hyperactive excitability focus induced by means of concentrated strychnine solutions played the role of a determinant structure. The importance of the latter is in the fact that it determines the activity character of other epileptogenic foci, enhances their convulsive activity, unites them into a single functional complex and determines the behaviour of the complex as a whole. This complex can be destroyed by depression of the determinant focus activity. Switching off any dependent foci included into this complex fails to destroy that latter. Results of the investigations confirmed on the new model the general concept of the role played by the determinant structures in the brain activity.

Acute Disease↗