[Role of functional state of neuronal mitochondria of cerebral cortex in mechanisms of nootropic activity of neuroprotectors in rats with alloxan hyperglycemia].

The influence of citicoline, phenylpiracetam, pentoxifylline and N-phenylacetyl-L-prolylglycine on cognitive processes and functional state of mitochondria in the neocortex of alloxan-diabetic rats has been studied. The drug effects on cognitive processes were assessed using passive avoidance tests in the dark-light camera. Latent period and the number of animals with amnesia skill on 6th and 20th days of drug administration were recorded. Functional status of mitochondria was assessed by mitochondrial pore opening and mitochondrial transmembrane potential (Y) on 20th day. It has been established that course administration of phenylpiracetam, citicoline and to a lesser extent N-phenylacetyl-L-prolylglycine, but not pentoxifylline, improves the processes of learning and storing conditional skill. At the same time, the nootropic activity of studied drugs was comparable to their effect on the functional state of mitochondria in neocortical neurons in rats with chronic hyperglycemia. According to mitoprotective activity (prevention of opening of mitochondrial cyclosporin-A-sensitive pores and restoration of mitochondrial transmembrane potential), the maximum potential was observed for citicoline and phenylpiracetam, and the minimum--for pentoxifylline. The results point out the importance of mitoprotective properties in nootropic effects of studied drugs.

A study of the mechanisms for antiaggregant activity of pyrrolidone derivatives in rats with chronic hyperglycemia.

In rats with chronic alloxan-induced hyperglycemia, pramiracetam and phenylpiracetam (but not piracetam) had a strong antiaggregant effect that was mediated by various mechanisms of platelet aggregation modulation. The effect of pramiracetam is mainly realized via the inhibition of thromboxane A2 metabolism, while activity of phenylpiracetam is primarily associated with a normalizing effect on function of constitutive NO synthase in platelets and vascular endothelium.

[Study of acetylsalicylic acid role in the potentiation of antiamnesic and neuroprotective properties of piracetam in rats with alloxan diabetes].

It has been established that prolonged alloxan-induced hyperglycemia in rats potentiates amnesic properties of scopolamine hydrobromide. It was characterized by shortening of the latent period by 44% (p<0,01) and by 47,7% (p<0,05) after 24 hours and on the 20th day of conditioned passive avoidance test. This effect was accompanied by increase in oxidative modification of proteins and nitric oxide synthesis in the cerebral cortex. Along with this, a significant enhancement of ADP- and collagen-induced platelet aggregation was observed. These processes may play the leading role in the development of cognitive deficit in diabetes. Meanwhile, co-administration of piracetam with acetylsalicylic acid was accompanied by an expressed antiamnetic potential - the reduction of early markers of proteins degradation (aldehydephenylhydrazones, APH) by 21,7% (p<0,05) and late markers of proteins degradation (ketonephenylhydrazones, KPH) by 23,8% (p<0,001) was noted. This combination was 15,7% (p<0,05) more active than piracetam according to the effect upon KPH. NO2-/NO3- level was also decreased by 30,3% (p<0,05) in comparison with alloxan-diabetic rats. The significant anti-platelet effect was observed: degree of collagen-induced platelet aggregation was reduced by 56,8% (p<0,01), ADP (5 µmol/l)-induced - by 31,7% (p<0,01), ADP (20 µmol/l)-induced - by 47,3% (p<0,01) as compared to the hyperglycemic rats. Such an increase in nootropic activity of piracetam may be assumed to be directly related to the ability of acetylsalicylic acid to improve microcirculation in the ischemic areas of the brain in diabetes and probably to its neuroprotective potential.

[Platelet hyperreactivity and antiaggregatory properties of nootropic drugs under conditions of alloxan-induced diabetes in rats].

The effects of nootropic drugs (noopept, pentoxifylline, piracetam, pramiracetam, Ginkgo biloba extract, entrop, cerebrocurin and citicoline) on platelet aggregation in rats with experimental diabetes have been studied. It is established that all these drugs exhibit an inhibitory action of various degrees against platelet hyperreactivity under conditions of chronic hyperglycemia. The maximum universality of the antiaggregatory action is characteristic of pramiracetam, entrop and Ginkgo biloba extract.

[Neuromediator analysis of sleep, analgesia and amnesia--components of general anesthesia with ketamine and thiopental sodium]. / Neiromediatornyi analiz sna, analgezii i amnezii--komponentov obshchei anestezii ketaminom i tiopental-natriem.

In experiments on rats the involvement of neuromediator systems into the development of outer manifestations of general anesthesia with ketamine and thiopental sodium was determined by the ability of neuromediator analyzers to change significantly their absolute values. The role of neuromediator mechanisms in general ketamine anesthesia can be determined by opiate-, serotonin-, GABA- and alpha 2-adrenomimetic, as well as alpha 1 and beta-adrenoblocking, anti-dopamine and anticholinergic properties of the anesthetic. The role of neuromediator systems in general anesthesia with thiopental sodium is determined by GABA-mimetic, antiadrenergic (alpha 2-agonist and alpha 1- and beta-adrenoceptor antagonist), anticholinergic and antidopaminergic properties of the thiobarbiturate.

[The effect of general anesthesia on memory in experimental animals]. / Vliianie obshchego obezbolivaniia na pamiat' v éksperimente.

Full recovery of short-term memory (maximum time of delayed reactions) and of the structure of situational conditioned reflex and differentiation inhibition in dogs is observed in 1.5-2.5 h after tranquil-anaesthesia (diazepam-ketamine in doses of 0.3-15 mg/kg correspondingly) and dissociative anaesthesia by ketamine (15 mg/kg) in 6-8 h after neuroleptanalgesia (droperidol-fentanyl 2.5-0.05 mg/kg correspondingly), 20-24 h after narcosis by thiopental sodium (30 mg/kg) and by the end of the 3d day after neuroleptanaesthesia (droperidol-ketamine 2.5-15 mg/kg correspondingly). The recovery of the reaction of memory trace reproduction (of conditioned reaction of passive avoidance in rats) after various types of general anaesthesia is observed mainly in the same sequence, but on the average a day later than the short-term memory in dogs.

[GABA-ergic mechanisms of the action of ketamine on the structures of the hippocampo-reticulo-neocortical system of the brain]. / Issledovanie GAMK-ergicheskikh mekhanizmov deistviia ketamina na struktury gippokampo-retikulo-neokortikal'noi sistemy mozga.

In freely mobile rabbits with electrodes preliminarily implanted in the brain structures ketamine (5 mg/kg intravenously or 20 mg/kg intramuscularly) exhibited properties of GABA receptor agonist decreasing the direct excitability of the mesencephalic reticular formation and periaqueductal gray matter and reducing their activating effect on the frontal cortex (FC) and dorsal region of the hippocamp (DH). GABA-mimetics (muscimol, baclofen, aminooxyacetic acid) as well as GABA system antagonists (bicuculline, thiosemicarbazide) attenuated ketamine action at the level of DH and especially FC.

[Neurophysiological mechanisms of the action of GABA-tropic agents on brain structures]. / Neirofiziologicheskie mekhanizmy deistviia GAMK-tropnykh sredstv na struktury golovnogo mozga.

The effect of systemic administration of agonists and antagonists of GABA system on excitability and intracentral relationships of the brain structures was found during chronic experiments on rabbits with bipolar electrodes implanted in the region of the frontal cortex, dorsal hippocampus, midbrain reticular formation and central gray matter. The changes of the functional state of the cerebral formations were suggested to be related to a different degree of the involvement of GABA receptors of types A and B.

[GABAergic mechanisms of the function of hippocampal-reticulo-neocortical system structures of the brain under thiopental anesthesia]. / Izuchenie GAMK-ergicheskikh mekhanizmov funktsionirovaniia struktur gippokampo-retikulo-neocortikal'noi sistemy mozga v usloviiakh tiopentalobogo narkoza.

In experiments on rabbits with electrodes chronically implanted in the brain structures thiopental exhibited properties of a pronounced GABA receptor agonist. Muscimol potentiated the suppressive effect of the general anesthetic agent on electrographic and behavioral correlates of excitability of the periaqueductal gray matter, mesencephalic reticular formation and especially dorsal hippocampus and frontal neocortex. On the contrary, bicuculline reduced the anesthetic effect of thiopental but potentiated the inhibitory action of the cortex and hippocampus on the midbrain formations as compared with the effects of the barbiturate proper.

[Role of cholinergic and adrenergic mechanisms in the action of ketamine and thiopental sodium on the structures of the hippocampal-reticular complex and the neocortex]. / Rol' kholinergicheskikh i adrenergicheskikh mekhanizmov v deistvii ketamina i tiopental-natriia na struktury gippokampretikuliarnogo kompleksa i novoi kory mozga.

Under conditions of free behaviour of rabbits with electrodes implanted into the brain structures it was found that ketamine and sodium thiopental decrease the excitability in the dorsal hippocamp, reticular formation and periaqueductal gray matter of the midbrain. Excitability of the frontal neocortex increases during general anesthesia with ketamine and decreases during thiopental narcosis. Changes in excitability of the studied cerebral structures during general anesthesia can be determined by common N-cholinoblocking and alpha-adrenomimetic properties of ketamine and thiopental at the level of the dorsal hippocamp, cholinoblocking and adrenoblocking properties at the level of the reticular formation and central gray matter. In the frontal cortex ketamine presented properties of an M-cholinomimetic and adrenomimetic agent, sodium thiopental--those of a M-cholinoblocker and beta-adrenoblocker.

[Role of cholinergic mechanisms in the action of sodium oxybutyrate on the structures of the hippocampus-reticular complex and of the neocortex]. / Rol'kholinergicheskikh mekhanizmov v deistvii natriia oksibutirata na struktury gippokamp-retikuliarnogo kompleksa i novoi kory mozga.

It has been established in chronic experiments on rabbits that accumulation of endogenous acetylcholine (galanthamine--1 mg/kg) prevents the development of sodium hydroxybutyrate (500 mg/kg) ability to increase the excitability of the mesencephalic reticular formation and to reduce the level of frontal cortex excitability. Inhibition of the central muscarinic (metamizyl--2 mg/kg) or nicotinic (eterofen--10 mg/kg) cholinoreceptors prevents the stimulant action or sodium hydroxybutyrate on the excitability of the dorsal hippocamp and mesencephalic reticular formation. Blockade of the central N-cholinoreceptors changes the marked effect of sodium hydroxybutyrate on the blood content of the test brain structures. This may attest to the participation of N-cholinoreceptors in the effects of sodium hydroxybutyrate.

[The influence of fluothane and hexobarbital on the cerebral cortex and spinal cord centers]. / Bliianie ftorotana i Geksenala na kiru bol'shikh polusharii i tsentry shinnogo mozga.

Tests set up on 17 cats demonstrated by using methods of evoked potentials that the reflex activity of the spinal cord centers is inhibited after introduction of 2.3 +/- 0.2 ml of fluothane, whereas the functional performance capacity of the large hemispheres cortex is suppressed following administration of 3,2 +/- 0,8 ml of the drug. The restitution of excitability and conductivity of the cortex in the post-anesthetization period proceeds at the rate 1.7 times faster than the restoration of the spinal cord centers. With deepening of the hexobarbital anesthesia complete inhibition of the spinal reflex activity supervenes after introduction of 56.3 +/- 12.3 ml/kg and that of the cortex following introduction of 115.0 +/- 23.2 ml/kg of hexobarbital.