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Biomedical subjects

K S Raevskiĭ

Publications and source records attributed to K S Raevskiĭ.

At least 19 recordsLinked to original sources

[The interstrain differences in the effects of D-amphetamine and raclopride on dorsal striatum dopaminergic system in KM and Wistar rats (microdialysis study)].

The levels of dopamine (DA) was determined by intracerebral microdialysis in vivo in KM rats selected for high audiogenic epilepsy, and in Wistar rats selected for nonsusceptibility to loud sound. The basal level of dopamine was 25% higher in the KM rats (P < 0.05). A single amphetamine injection (1 mg/kg body weight, intraperitoneously) caused a significant increase in the DA basal level up to 250-260% in animals of both genotypes. However, in Wistar rats, the level of DA reached maximum as soon as 20 min after amphetamine administration, whereas in KM rats, this happened only after 120 min. After a single injection of the antagonist of D2 and D3 dopamine receptors raclopride (1.2 mg/kg of body weight, intraperitoneously), an increase in the level of DA was similar in amplitude in rats of both genotypes (up to about 210%); however, this occurred 20-30 and 100 min after raclopride administration to Wistar and KM rats, respectively. This evidence suggests that the genetic defect of KM rats, namely, the high level of audiogenic epilepsy, is caused by abnormalities of the neuromediator brain systems and presumably accompanied by the regulatory gene dysfunction.

Amphetamine↗

[Dopamine synthesis by non-dopaminergic neurons of the rat fetus arquate nucleus].

Our hypothesis was tested in respect to dopamine synthesis by non-dopaminergic neurons expressing individual complementary enzymes of the DA synthetic pathway. According to the hypothesis, L-dihydroxyphenylalanine (L-DOPA) synthesised in tyrosine hydroxylase(TH)-expressing neurons for conversion to dopamine. The mediobasal hypothalamus of rats on the 21st embryonic day was used as an experimental model. The fetal substantia nigra containing dopaminergic neurons served as control. Dopamine and L-DOPA were measured by high performance liquid chromatography in cell extracts and incubation medium in presence or absence of L-tyrosine. L-tyrosine administration increased L-DOPA synthesis in the mediobasal hypothalamus and substantia nigra. Moreover, L-tyrosine provoked an increase of dopamine synthesis in substantia nigra and a decrease in the mediobasal hypothalamus. This is, probably, due to an L-tyrosine-induced competitive inhibition of the L-DOPA transport to monoenzymatic AADC neurons after its release from the monoenzymatic TH neurons. This study provides a convincing evidence of dopamine synthesis by non-dopaminergic neurons expressing TH or AADC, in cooperation.

Animals↗

[Allosteric modulators of AMPA type glutamate receptors a novel gubclass of physiologically active substances].

Properties of AMPA type glutamate receptors widely presented within mammalian central nervous system are reviewed. AMPA receptors belong to ionotropic subclass of glutamate receptors and participate in fast excitatory glutamatergic transmission in the brain. Molecular structure of AMPA receptors consists of several subunits (GluRA1-GluRA4), which display various sensitivity to receptor ligands. These receptors are named according to their selective agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). AMPA receptor modulators represented by several chemical groups: pyrrolidinones (aniracetam), benzothiodiazinedioxides, benzylpiperidines and biarylpropylsulphonamides. These compounds facilitate AMPA receptor-mediated glutamatergic neurotransmission. AMPA receptor modulators enhance cognitive functions (learning and memory), reveal anxiolytic and antidepressant action, suppress the effects of psychostimulant agents, potentiate the effects of antipsychotic drugs, display neuroprotective properties. Positive modulation of AMPA receptor-associated ionic channels was shown to underline the mode of action of these substances that results in enhancement of long-term potentiation (LTP) and increasing neurotrophic factors expression. Preliminary clinical results have shown positive therapeutic effect of these substances in patients with cognitive impairment.

Animals↗

[Dizocilpine inhibits suppression of c-fos gene by delta-sleep peptide in the rat hypothalamic paraventricular nucleus].

The effects of intracerebroventricular administration of the non-competitive NMDA-receptor blocker Dizocilpine (MK-801) on delta sleep-inducing peptide (DSIP) suppression of c-fos induction, were studied. The data obtained indicate that preliminary i.c.v. MK-801 injection inhibits immediate early gene c-fos suppression by DSIP in the parvocellular paraventricular hypothalamus.

Animals↗

[Features of neurotransmitter pool in cerebrospinal fluid of patients with epilepsy].

The paper deals with the state of neurotransmitter pool in cerebrospinal fluid of epileptic patients. There were significant peculiarities of the dynamics of both excitatory (glutamate, aspartate) and inhibitory (GABA, glycine, taurine) neurotransmitters in respect of the severity of the pathologic process, frequency and type of convulsive seizures. The correlation found between a degree of the disease severity and a level of glutamate in cerebrospinal fluid after the seizures and between them could be a criterion for the prognosis of epilepsy.

Adult↗

[The role of nitric oxide in brain glutaminergic pathology].

Nitric oxide (NO) is highly reactive signal molecule that is widely distributed in the body, and in the mammalian brain in particular. The agent is a gaseous chemical messenger that acts as a universal modulator of a diversity of physiological functions, such as interneuronal communications, synaptic plasticity, memory formation, receptor functions, intracellular signal transmission, mediator release. NO is assumed to be a key pathological agent due to its neurotoxic effect in developing neurological disorders, such as ischemia, cerebral stroke, epileptiform seizures. The agent is shown to be significantly increased in the brain of rats with abnormalities.

Animals↗

[Pharmacological modulation of dopaminergic transmission in the rat striatum in vivo].

Inhibition of catechol-0-methyltransferase (COMT) activity by Tolcapone was shown to result in increase of the striatal DA extracellular content in unrestrained rats pretreated with L-3,4-dihydroxyphenilalanine combined with Carbidopa, the decarboxylation inhibiting agent. Tolcapone enhanced the increase of the DA level in the rat striatal dialysates produced by treatment of these animals with specific DA re-uptake blocker GBR 12909. The latter elicits stereotype behaviour in rats that is substantially enhanced by tolcapone. The DA turnover rate in the striatum was decreased by the GBR 12909. The data obtained suggest that the DA transporter of neuronal membrane plays a major role in the neurochemical homeostasis at synaptic level.

Animals↗

[Neuroprotective effects of glycine in the acute period of ischemic stroke].

Both the efficiency of glycine in the acute period of hemispheric ischemic stroke and mechanisms of its action were studied in a double blind placebo-controlled trial including 200 patients. Orgogozo's and Scandinavian scales for objective assessment of the condition severity and of a degree of neurologic deficiency, and Bartel's scale--for evaluation of functional recovery were used and measurements were made of the levels of autoantibodies to the structural component of glutamate NMDA-receptors in blood serum and concentrations of neurotransmitter amino acids and of the products of lipid peroxidation in cerebrospinal fluid. Sublingual glycine application in daily dose of 1-2 g was found effective beginning with the first 6 hours of the stroke development during 5 days. Multicomponent neuroprotective action of glycine was established directed at correction of the unbalance between stimulating and inhibiting aminoacidergic neurotransmitters, as well as at a decrease of excitotoxicity and oxidant stress.

Acute Disease↗

[Levels of neurotransmitter amino acids in the cerebrospinal fluid of patients with acute ischemic stroke].

The dynamics of the levels of both excitatory (aspartate, glutamate) and inhibitory (GABA, glycine) neurotransmitter amino acids was estimated in cerebrospinal fluid of 110 patients with hemispheric ischemic stroke. A significant increase of the contents of glutamate and aspartate was found beginning with the first 6 hours of the disease onset. The degree and duration of such elevation correlated with severity of the stroke. Maximal GABA and glycine levels were registered to the end of the 1st day of the stroke, that reflected delayed triggering of the protective inhibitory mechanisms. It was established that insufficiency of GABA-mediation in hemispherical location of the stroke was much responsible for both the severity of its clinical manifestations and potential of the restorative processes. Early significant biochemical criteria for objective assessment of the severity of cerebral ischemia as well as of the stroke course and outcome were defined. The most unfavourable prognostic signs were low GABA concentration (or impossibility of its evaluation) during the first days of the stroke, progredient elevation of the aspartate level until the 3d day of the disease and the severe fall of glutamate concentration (in spite of its initial increase on the 1st day).

Acute Disease↗

[Nitric oxide in the rat cerebral cortex in seizure models: potential ways of pharmacological modulation].

Seizures induced with Thiosemicarbaside, Pentylenetetrasole, N-methyl-D,L-aspartate were used as models. The NO content increased 4-5-fold in the brain cortex at the peak of seizures. The increase could be prevented by pre-treatment with N-nitro-L-arginine and the seizures were weakened. Anticonvulsant drugs reduced the seizure manifestations and partially prevented the NO generation enhancement. The latter seems to be involved in pathophysiological mechanisms underlying the seizures.

Animals↗

[Functional role and pharmacological regulation of the dopaminergic system of the brain].

The dopaminergic systems of the brain are thought to play a major role in the regulation of motor, cognitive, neuroendocrine functions and in the pathogenesis of several pathological conditions, including neurodegenerative diseases, affective disorders, schizophrenia, drug addiction, etc. Functional, biochemical, and pharmacological heterogeneity of dopamine receptors, which were divided into D1-like (D1 and D5 subtypes) and D2-like (D2, D3, and D4) families of receptors, has been postulated. The paper concerns the recent advances in the study of the structure and function of two main dopaminergic brain systems, i.e. nigrostriatal and mesolimbic. The problem of autoreceptor regulation of dopaminergic neurotransmission, particularly the processes of dopamine synthesis, release, and metabolism is discussed. The involvement of D2 and D3 dopamine autoreceptors in the control of these processes and differences in the mode of action of typical neuroleptics are analyzed. It is hypothesized that dopamine D3 autoreceptor is preferentially involved in the regulation of dopamine release while D2 one is responsible for the control of dopamine synthesis and metabolism in rat basal ganglia in vivo.

Animals↗