[Simulation of repeated local hemorrhagic stroke in rats].

The processes of developed in CNS the complicated stroke and developments of fittings for their pharmaceutical therapy were developed and offering by standardized method of the experimental secondary stroke in rats, suitable for the use in sharp and chronic researches. Variant of repeated hemorrhagic stroke consist of autohemorrhagic right hemisphere stroke by the mechanical damage of brain tissue after 10-daily occlusion of right common carotid artery was studied. A model is comfortable for reproducing of the repeated standardized local damage of brain, is more adequate form of design of transient and chronic cerebrovascular pathology, than the independent use of local hemorrhage of autoblood in the brain of animals. The morphological description of model approaches the clinical variants of development and flow of sharp hemorrhagic stroke after a previous chronic cerebral insufficiency on an ischemic type.

[Influence of cortical neurotrophic factors on the neurocytokine production system in acute hemorrhagic stroke].

The mechanism of therapeutic action of cortical neurotropic factors (CNTF) was studied in hemorrhagic stroke. In intracerebral hemorrhage, CNTFs were shown to elevate the level of nerve growth factor mRNA and at the same time, produce no effect on its level in intact animals. The neuroactivating action of CNTF in the acute phase of hemorrhagic stroke was achieved by intranasal administration due to the retrograde axon transport of CNTF molecules along the olfactory nerve fibers to the brain, by passing the blood-brain barrier. It was ascertained that the molecules of tritium-labeled CHTF accumulated in the central nervous system following 20 minutes and the level of label accumulation is proportionally increased after 120 minutes. The pattern of accumulation of the intranasally administered label in the olfactory tract and olfactory bulb proves CNTF transportation along these structures of the nervous system. Therefore, when intranasally administered, CNTFs are able to transport to the central nervous system along the olfactory tract and to enhance the expression of nerve growth factor mRNA in hemorrhagic stroke.

[Procedures for modeling of hemorrhagic stroke].

Hemorrhagic stroke (intracerebral hemorrhage) is a socially significant cerebrovascular disease. Despite high mortality and disability rates, hemorrhagic stroke has been experimentally studied to a lesser extent than ischemic stroke. The modeling of hemorrhagic stroke may be used to solve a number of fundamental and practical problems. The present review deals with the review of the currently available procedures for modeling hemorrhagic stroke.

[Cytoprotective effect of neuropeptides on immunocompetent cells (in vitro study)].

Effects of the nootropic neuropeptide drugs cerebrolysin (Ebewe, Austria) and cortexin (Geterofarm, Russia) on the immunocompetent cells (T-lymphocytes of the MT-4 cell line and B-lymphocytes of the Raji cell line) were studied in vitro. The cell viability was evaluated using the MTT test by counting living and dead cells upon incubation under various conditions with a vital stain (Trypan Blue). It is established that cerebrolysin exhibits cytoprotective properties with respect to both T- and B-lymphocytes and favors the survival of immunocompetent cells. In addition, cerebrolysin in certain concentrations produces a proliferative effect on B-lymphocytes, thus stimulating the formation of immune memory B cells. In contrast, cortexin in certain concentrations produces a cytotoxic and antiproliferative action on T-lymphocytes. The parameters of influence for both drugs depend on their concentration in the cell incubation medium, the duration of action, and (most significantly) the cell type. These properties may account for one of the possible mechanisms of the immunoprotective action of cerebrolysin in various neurological states accompanied by immune response disorders.

[The role of latent virus infection of the central nervous system in acute hemorrhagic stroke].

The purpose of the investigation was to study whether latent virus infection may activate in the murine brain using a model of hemorrhagic stroke. Acute intracerebral hemorrhagic stroke was induced in the internal capsule in accordance with the original technology. For experimental reproduction of virus meningoencephalitis, albino mice were infected with a sublethal dose of herpes simplex virus. The investigation ascertained persistent virus activation, as shown by the polymerase chain reaction technique that detected herpes simplex virus type 1 in the blood and brain of the animals, as well as the development of a cerebral inflammatory lesion associated with acute hemorrhagic stroke. The findings suggest that encephalitis may develop in acute stroke due to herpes simplex virus reactivation from the latent state, which will improve monitoring and treatment quality in acute stroke.

[Dynamics of neurodegenerative processes and lifespan under the action of Cerebral combined with other pharmaceuticals in Drosophila melanogaster mutants].

Effective influence of the drug Cerebral and its micro- and macrofractions on the mean lifespan and degenerative process dynamics of Drosophila melanogaster have been investigated. No dose--effect dependence was detected when different concentrations of Cerebral were used. The administration of Cerebral as a neuroactivating remedy combined with piracetam and verapamil was most effective, leading to an increase in the lifespan and a delay in the appearance of brain degenerative processes.

[Rat immunoreactivity in experimental modeling of acute autohemorrhagic bihemispheric stroke in the presence of staphylococcal infection].

Experimental studies were made of rat immunoreactivity in experimental modeling of acute hemorrhagic stroke in staphylococcal infection. Bactericidal activity and reserve bactericidal activity of neutrophils in NBT-test enhance while mid-molecular CIC level decreases because of phagocyte activation. ABA high titers in blood reflect activation of autoimmune processes. Splenic mass increased suggesting activation of proliferation of splenic lymphoid cells or enhanced migration of immature lymphoid cells from bone marrow to the spleen. Experimental animals had suppressed functional activity of main lymphoid cells populations in blast-transformation reaction which may affect the course of early recovery, promote activation of infectious bacterial process, autoaggression. The results of the studies can serve the basis for further investigations of immune mechanisms involved in development of hemorrhagic stroke in the presence of infectious process.

[Effects of neuropeptides on interferon production in vitro].

The study of an interferon-inducing action of neuropeptides (a cerebrolysin model) on production of interferons by human blood leukocytes has shown that neuropeptides induce gamma-interferon production in the titer 267 IU/ml that determines one of the mechanisms of a neuroimmunocorrecting effect of cerebrolysin (Ebewe, Austria) in many neurological diseases (acute stroke, brain traumas and different neuroinfectious diseases).

[Neuroimmunocorrection therapy for the prophylaxis of infectious complications in acute stroke patients].

Neuroimmunocorrection therapy with cerebrolysin has been used for the prophylaxis of clinical pneumonia development in the early stage of acute stroke in a group of 140 patients with heavy clinical course of acute ischemic stroke (AIS). All patients in the test and control groups received the basal anti-AIS therapy and antibacterial drugs (IV-generation cephalosporins) in case of pneumonia development. The efficacy of cerebrolysin administration was evaluated both on the clinical scale (NIH-NINDS, CPIS, SIRS immonograms) and using laboratory indices. It is established that the proposed neuroimmunocorrection therapy with cerebrolysin decreases the frequency of the clinical pneumonia development. A relationship between the pneumonia onset rate and the focus localization in limbico-diencephalic part of the brain is established. The use of cerebrolysin decreases lethality, normalizes the impaired immunity indices, accelerates the restoration of violated neural functions, suppresses pneumonia development, restores the level of albumin, and normalizes the laboratory indices of inflammatory syndrome.

[Development of encephalitis in modeling of acute hemorrhagic stroke--a new variant of a somatic complication].

We studied immunological and morphological changes in rat brain in an acute period of experimental hemorrhagic stroke (HS). The latter was induced mechanically by the method of A. N. Makarenko et al (the area of destruction in the rat brain was 0.15-0.2 mm3 in the internal capsule (c.i.) of both hemispheres) in 105 noninbred white male and female mice (body mass 18-22 g) and 20 Wistar rats (body mass 200-220 g). The rats were decapitated on day 1, 3, 10. HS modeling in mice is accompanied with immune disorders: high production of hemagglutinating antibodies in parallel with low titer of hemolysines, significant reduction of thymic mass and intensification of delayed type hypersensitivity. Besides changes typical for an acute period of HS, histological studies of the brain revealed encephalitic lesions located both near HS foci and far from them in 10 test animals of 14 on days 3-10. We observed signs of productive ependymitis and focal vasculitis (capillaritis). The infiltrates consisted primarily of microglyal cells and lymphocytes. In the controls such changes occurred in 1 of 6 rats. The results show that in an acute period of HS in rats their brain may be affected with activated latent infection and encephalitis. The same phenomenon may be observed in humans.

[Complex influence of pharmacological agents on degenerative processes in brain of Drosophila melanogaster mutants].

A scheme of complex administration of drugs in the order neuroprotector + neuroactivator + neuroretarder for the treatment of neurodegenerative processes in the brain has been elaborated and tested on a model object representing neurodegenerative mutants of Drosophila melanogaster. The appearance of changes in the brain was delayed when drugs were used separately: donepezil hydrochloride (arisept), 10 - 11 days, epinephrine and nimodipine, 1 - 2 days. The treatment of flies with the same drugs in the order arisept + epinephrine + nimodipine leads to the complete regeneration of D. melanogaster brain tissue to within 15 days of imago life.

Effect of active fraction of cerebral on expression of caspase-3 and beta-amyloid precursor protein during therapy of hemorrhagic stroke in the acute and delayed periods.

Active anti-stroke fraction of Cerebral preparation (extract of water-soluble molecules from brain tissue of animals with hemorrhagic stroke) decreased caspase-3 expression and improved survival of experimental animals in the acute period after hemorrhagic stroke.

[A comparative study of antistroke activity of the new drug "cerebral" and its fractions in rats].

The effect of the new drug "cerebral" and its fractions 1-3 on the model of bilateral hemorrhagic stroke in white rats was studied with reference to the action of cebrolysin and cerebrolysate-M. With respect to the general functional state, behavioral activity restoration, and morphological data, the most pronounced antistroke action was observed for the cerebral-1 fraction. This fraction was further separated into three subfractions. The most promising test results were obtained for the 1.2 subfraction, which was selected for the further investigation.

[Neuroactivating mechanism of action of the new trophinotropic drug cerebral]. / Neiroaktiviruiushchii mekhanizm trofinotropina tserebrala.

The new drug cerebral, as well as its low-molecular-weight (LMW) fraction (MW, < or = 500 Da) separated from a ready-to-use commercial form of this new neutrotropic drug, increases the level of synthesis and secretion of the nerve growth factor (NGF) in rats under conditions of experimental hemorrhagic stroke (HS), while not influencing the NGF synthesis and secretion in intact animals. This neuroactivating effect of the trophinotropic drug cerebral and its LMW fraction in the acute HS development stage was observed upon intranasal administration. In comparison with parenteral (intraperitoneal) administration, the intranasal introduction provides for the optimum drug delivery to the CNS bypassing the blood-brain barrier. Trophinotropic agents are a new class of drugs with neuroactivating mechanism of action upon the NGF synthesis and secretion under HS conditions.

[Dynamics of distribution of the low molecular weight fraction of cerebral in rat tissues upon intranasal administration]. / Dinamika raspredeleniia nizkomolekuliarnykh veshchestv tserebrala v tkaniakh krys pri intranazal'nom vvedenii.

A homogeneous low-molecular-weight fraction (MW, 350-500 Da) separated from a ready-to-use commercial form of the new neurotropic drug cerebral (for amino acid composition see Arkh. Psikh. 3(18), 138-143 (1998)) increases the survival of experimental rats upon experimental hemorrhagic stroke (HS). The distribution and accumulation of tritium-labeled preparation was studied in various tissues (tractus olfactorius, bulbus olfactorius, damaged neocortex region, hippocampus, hypothalamus, midbrain, pons, medulla oblongata, cerebrum, liver) and in the blood of intact, shame-operated (SO), and HS rats 20 and 120 min after intranasal administration. A significant amount of the labeled drug is accumulated for 20 min in all structures of the brain, liver, and blood. After 120 min, the level of accumulated drug proportionally increases. The amount of labeled preparation accumulated in SO and HS rats is greater than that in intact rats. The character of cerebral accumulation in tractus olfactorius and bulbus olfactorius upon intranasal administration is indicative of the effective drug transport to CNS via these pathways. Therefore, the intranasal administration can offer a promising means of clinical treatment of HS patients.

[Effect of nooglutil on rats with intracerebral posttraumatic hematoma (hemorrhagic stroke)]. / Effekt noogliutila u krys s intratserebral'noi postravmaticheskoi gematomoi (gemorragicheskim insul'tom).

The effect of the new nootropic drug nooglutyl, a positive modulator of AMPA-subtype glutamatergic receptors, was studied in rats with a model hemorrhagic stroke (HS)--posttraumatic hematoma induced by cerebral tissue destruction in the capsule interna region. Single intraperitoneal injections of nooglutyl (10 and 20 mg/kg) 3-4 h after operation decreased the HS-induced neurological deficiency, restored the coordination of movements, improved the passive avoidance reaction retrieval, and prevented the loss of experimental animals. The results show evidence of a pronounced neuroprotector action of nooglutyl in rats with the HS model.

[Effect of Cerebral on the immune system in experimental hemorrhagic stroke]. / Vliianie tserebrala na immunnuiu sistemu pri éksperimental'nom gemorragicheskom insul'te.

Data on the development of three experimental models of hemorrhagic stroke in mice are reported. The models differ in the extent of damage. From the standpoint of the immunopharmacological investigation, most adequate model is provided by the light acute brain circulation disorder (LABCD). In the LABCD model, the hemorrhagic stroke is characterized by reduction in the thymus weight, inhibition of the antibody (hemolysin) synthesis, and enhancement of the delayed type hypersensitivity response. The new antistroke drug cerebral decreased (especially after intranasal administration) the level of lethality in experimental animals and improved the immunological indices.

[Antihypoxic activity of the novel intraorganoid pharmacological preparation mitochondrin]. / Antigipoksicheskaia aktivnost' novogo intraorganoidnogo farmakologicheskogo sredstva mitokhondrina.

The antihypoxant and membranoprotector properties of the new intraorganoid pharmacological preparation mitochondrin (M-1) were studied in two series of experiments. In the first series, the drug activity was studied on a model of hypoxia with hypercapny; in the second series, the drug was tested on a model of hemic hypoxia caused by neurotoxic damage (acute nitrobenzene intoxication). It was established that M-1 (obtained from the brain tissue of newborn rabbits) possesses antihypoxant activity, which is manifested in both hypoxia--hypercapnia and hemic hypoxia. The drug effect was more pronounced 3 h after administration than on the next day. The antihypoxant action of M-1 is related to the cytomembrane neuroprotector activity.

[Simulation of local cerebral hemorrhage in different brain structures of experimental animals]. / Metod modelirovaniia lokal'nogo krovoizliianiia v razlichnykh strukturakh golovnogo mozga u éksperimental'nykh zhivotnykh.

A standardized experimental model of intracerebral hemorrhagic stroke in small laboratory animals is developed and advanced for chronic neurobiological studies of normal and pathological higher nervous activity as well as disorders developed after acute hemorrhages. A device is advanced which allows a researcher to destroy appropriate brain structures (tissues and local blood vessels) with necessary precision by four-six rotations of curved stereotaxically inserted mandrel-wire knife and, subsequently, to inject autoblood into the area of the lesion. The advanced model is convenient for the reproduction of lesions in different brain regions (for the purpose of experimental knockouts) in neurophysiological, neuropharmacological, and clinical investigations.

[The hypotensive effect of compression action on the chest cavity in patients with arterial hypertension]. / Gipotenzivnyi éffekt kompressionnogo vozdeistviia na grudnuiu kletku u bol'nykh s arterial'noi gipertenziei.

Effect were studied of a dosed chest compression on the arterial pressure (AP) in stage I-II hypertensive disease. AP was recorded at all procedures, during the whole time the respective procedure was being conducted and during five days following the course of treatment. A significant hypotensive effect was recordable in the wake of chest compression.