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Biomedical subjects

V P Chekhonin

Publications and source records attributed to V P Chekhonin.

At least 19 recordsLinked to original sources
PubMed2006

[Elimination of neurospecific proteins from CNS: pathogenetic and methodical aspects].

Appearance of neurospecific proteins (NSP) outside the brain plays a certain pathogenetic role in the development of autosensitization occurring in many kinds of CNS injuries and diseases. Analysis of modern views of cerebrospinal fluid (CSF) exchange allows us to suppose that NSP are eliminated from the brain tissue within CSF, moving from the subarachnoid space into cranial veins, and by lymphatic way, into deep cervical lymph nodes. Elevation of NSP level in CSF indicates an actual neudegenerative process. Serum levels of NSP are determined by the balance between the elimination of NSP from the brain, on the one hand, and their metabolism and the response of the immune system to the appearance of these autoantigenes in the blood stream, on the other. Basing on their own data on the dynamics of NSP (NSE, GFAR, and MBP) concentrations and the proportions of these proteins in CSF and serum (coefficient of elimination) in rats after ischemic, hypoxic, and autoimmune cerebral lesions, the authors offer an algorithm of pathogenetic evaluation, including, on the one part, a conclusion on the presence or absence of a neurodegenerative process, and, on the other, a conclusion on a normal or lowered rate of NSP elimination (metabolism). The results of such an analysis may have a clinical significance in terms of the development of a pathogenetic therapy, including, in every individual case, not only neuroprotectors, but also pharmaceuticals directed towards correction of the functional condition of the immune system.

Animals↗
PubMed2006

[Direct drug delivery to the brain].

The authors of the review discuss the present-day state of and promising approaches to directed delivery of biological agents into the brain. Special attention is drawn to micellar and liposomal transport through the blood-brain barrier (BBB) targeted by immunochemical vectors, such as native or hydrophobized antibodies to specific antigens located at the BBB or in the brain parenchyma.

Biological Transport↗
PubMed2005

Culturing of specialized glial cells (olfactory ensheathing cells) of human olfactory epithelium.

A monolayer of dissociated glial cells of human olfactory epithelium was cultured in Petri dishes and 12-well plates using a polylysine-laminin substrate. Primary cultures were subcultured after 10-15 days. The cell cultures were analyzed by phase contrast microscopy at all stages of culturing. A cytological study involved histological methods (trypan blue staining) and immunocytochemical visualization of GFAP, nestin, and low-affinity nerve growth factor receptors. At the final stage of culturing (5 passages) the monolayer cultures included 2 types of cells: GFAP- and p75-positive glial cells and nestin-positive fibroblasts.

Cells, Cultured↗
PubMed2004

Selective accumulation of monoclonal antibodies against neurospecific enolase in brain tissue of rats with middle cerebral artery occlusion.

Preparations of I(125)-labeled monoclonal antibodies against neurospecific enolase and mouse plasma IgG1 were injected intravenously to rats immediately after unilateral occlusion of the middle cerebral artery. Radioactivity of I(125)-labeled monoclonal antibodies against neurospecific enolase in the brain tissue progressively increased, reached a maximum by the 48th hour, and remained practically unchanged after 72 h. At the same time radioactivity of labeled IgG1 in the brain tissue and radioactivity of both preparations in the blood, liver, spleen, kidneys, heart, and lungs decreased over 72 h. Selective accumulation of I(125)-labeled monoclonal antibodies against neurospecific enolase was less significant in the brain tissue of the contralateral hemisphere and cerebellum not exposed to ischemia.

Animals↗
PubMed2004

[Modeling of focal ischemia of the brain].

Methods of modeling and criteria of evaluating the pathological process in the central nervous system (CNS) as well as modern technologies of provoking the focal ischemia of the brain in experimental animals are under discussion. The results were analyzed comparatively from the viewpoint of efficiency and adequacy of certain models as well as of the clinical specificity of ischemic strikes in man and of set research goals. A literature analysis confirms that the existing arsenal of methodical schemes provides for choosing the most adequate model of focal ischemia of the brain and to ensure a cerebral infarction of a preset scope and localization; it makes possible also an objective evaluation of pathological processes occurring in the cerebral tissues both at the earliest stages of ischemic lesion and during a relatively long time period comparable with rehabilitation time period. Achievements in the sphere of experimental modeling of focal ischemia of the brain pave the way to further promotion of experimental therapy in acute stroke and open up new research priorities; it concerns primarily research of mechanisms timing the neurodegenerative process after ischemic stroke as well as searching-for and testing of means of stroke prevention and of patients' rehabilitation.

Animals↗
PubMed2004

[Liposome-oriented transport of therapeutic drugs].

The attempts to use liposomes as containers for the transport of therapeutic drugs have been undertaken during the recent 40 years. However, the first success was achieved only in the 80-ies, when the sterically stabilized liposomes were invented. It was found that the liposome biological layer modified through, adding to it, certain polymers prolonged the blood circulation and reduced the capture of liposomes by RES cells. Elaboration of immunoliposomes, i.e. those conjugated with antibodies, was the next step in the path of perfecting the liposomes as a transport tool for the sake of binding with target-cells and to ensure the address-oriented delivery of drugs to a pathology focus. Preclinical and clinical testing of liposome-form of antitumor drugs witnessed to their lower toxicity and better pharmacokinetic indices; besides, they selectively accumulate themselves in tumor cells and have a more pronounced therapeutic effect even at lower doses of drugs in case of tumors resistant to the already made chemotherapy.

Animals↗
PubMed2003

Ketamine-induced rotational asymmetry in evaluation of motor disturbances in rats with middle cerebral artery occlusion.

Intraperitoneal injection of ketamine in subanesthetic doses to Wistar rats with unilateral occlusion of the middle cerebral artery caused ipsilateral rotation (2-10 rpm), which was recorded in an automatic rotameter. The optimal dose of ketamine was 50 mg/kg. The animals were examined in an automatic rotameter for 40 min. Motor asymmetry persisted for no less than 2 months after surgery. According to the neurological test (Menzies scale) motor asymmetry in animals with focal brain ischemia persisted for no more than 30 days. The degree of ketamine-induced motor asymmetry in intact rats was 0.10 0.03 rpm.

Animals↗
PubMed2003

Monitoring of neurological deficit and disturbances in higher nervous activity in rats with focal cerebral ischemia.

Neurological, locomotor, and behavioral changes in 20 Wistar rats with permanent proximal occlusion of the middle cerebral artery and 18 control sham-operated animals were monitored for 2 months at 10-day intervals. Neurological deficit was maximum immediately after occlusion (3.0 0.6 points), then progressively decreased, but did not completely disappear (0.70 0.06 points on day 60). In control animals neurological status returned to normal on days 10-15. The degree of ketamine-induced rotational asymmetry was 4.0 0.7 rpm over 40 days after surgery and decreased to 2.5 0.6 rpm on day 60. In control rats this parameter only transiently increased to 1.00 0.03 rpm (tdelta=2.5, p<0.05). The time of stay on a rotarod and the latency of passive avoidance in rats with focal cerebral ischemia were lower than in control animals throughout the experiment. The results of complex tests can be used in the experimental search for new drugs for the therapy and rehabilitation of stroke patients.

Animals↗
PubMed2003

Neurological deficit and disturbances in higher nervous activity during modeling of perinatal hypoxic-ischemic damage to the central nervous system in rat pups.

Seven-day-old Wistar rat pups were subjected to unilateral occlusion of the common cerebral artery and maintained in oxygen-low atmosphere. Neurological and behavioral changes were monitored for 12 weeks. The survival rate of treated animals was 90%. Body weight gain in these rats was lower than in the control. Neurological deficit was maximum 1 week after treatment and slightly regressed by the 12th week. Locomotor activity in treated rats was higher than in controls. Administration of ketamine in subanesthetic doses caused permanent ipsilateral rotational asymmetry in animals. Spatial disorientation and cognitive deficit in rats with hypoxic-ischemic damage to the central nervous system were revealed in passive avoidance, Y-maze, and rotarod tests. The total area of the hemisphere decreased, while the area of the lateral cerebral ventricle increased at the side of occlusion over the first 4-5 weeks of postnatal development. The size of the ipsilateral hemisphere remained low in adult animals.

Animals↗
PubMed2003

Enzyme immunoassay of NSE and GFAP as the criterion of dynamic evaluation of the rat blood-brain barrier in perinatal hypoxic ischemic injury of the CNS.

Enzyme immunoassay of the serum neurospecific antigens (gliofibrillar acid protein and neurospecific enolase) was used for evaluation of the resistance of the blood-brain barrier in Wistar rats with perinatal hypoxia and ischemia of the CNS. Perinatal hypoxia and ischemia of the CNS was modeled by two methods: ligation of the common carotid artery in 7-day-old rats followed by 3.5-h hypoxic hypoxia or 15-min anoxic exposure of fetuses isolated via hysterectomy on day 21 of gestation. Enzyme immunoassay of serum gliofibrillar acid protein and neurospecific enolase in control an experimental rat pups was carried out once a week during 3 months. In controls serum levels of gliofibrillar acid protein and neurospecific enolase virtually did not change during postnatal development, while in animals with cerebral hypoxia and ischemia induced in fetuses by both methods serum concentration of neurospecific enolase sharply increased 1 week after the injury and increased on weeks 6 and 10. The content of gliofibrillar acid protein was maximum on week 1 and later considerably varied, the peaks of its concentrations observed on weeks 3 and 8 preceded the increase in neurospecific enolase activity in peripheral blood.

Animals↗
PubMed2002

Comparison of the efficacy of cell preparations from embryonic ventral mesencephalon of various prenatal age transplanted intrastriatally to rats with 6-OHDA-induced Parkinsonism.

Cell preparations of ventral mesencephalon obtained from 8-, 14-, and 16-17-day rat embryos were stereotactically transplanted to homologous rats with 6-hydroxydopamine-induced hemiparkinsonism. Automated analysis of apomorphine-induced motor asymmetry for 3 months after neurotransplantation revealed higher efficacy of cell preparations from 8- and lower from 16-17-day-old embryos. These data correlated with histomorphological findings, in particular, with the size of grafts, glial reaction, and the number of dopaminergic neurons in the grafts.

Animals↗
PubMed2001

Immunoenzyme assay of glial fibrillary acidic protein for evaluation of functional activity of cell grafts from embryonic ventral mesencephalon in rats with experimental hemiparkinsonism.

The relationship between the release of glial fibrillary acidic protein (GFAP) into systemic circulation and the efficacy of transplantation of embryonic nervous tissue was studied on rats with 6-OHDA-induced hemiparkinsonism. It was found that intrastriatal transplantation of cell preparations from embryonic ventral mesencephalon significantly attenuated apomorphine-induced rotation, which points to functional recovery of the dopaminergic nigrostriatal system. The degree of this recovery depends on reactive astrogliosis around the graft and survival of dopaminergic neurons. Analysis of GFAP concentration revealed significant elimination of this antigen into the circulation 7 and 14 days after transplantation. In rats with good consolidation of the graft without pronounced reactive gliosis, the concentration of GFAP reached 253.99+/-79.30 ng/ml on week 4 after transplantation and decreased to 8.2+/-3.3 ng/ml 8-12 weeks after transplantation. In rats with poor graft consolidation associated with death of transplanted neurons and gliosis in the graft and surrounding tissue the concentration GFAP increased to 476.4+/-111.0 ng/ml within 4 weeks after transplantation and remained elevated (235.0+/-44.8 ng/ml) for 12 weeks. Thus, monitoring of serum GFAP concentrations allows in vivo evaluation of the functional state of intracerebral graft and the level of reactive gliosis. This test can be used for the prognosis of transplantation efficacy.

Animals↗
PubMed2001

Monoclonal anti-GFAP antibodies: extraction, characteristics, and immunoenzyme assay.

Methods of GFAP purification and obtaining of hybridoma cells producing monoclonal anti-GFAP antibodies and properties of GFAP preparation were described. The immunobloting data on specificity of obtained monoclonal antibodies are presented. A new method of GFAP immunoenzyme assay based on GFAP preparation and anti-GFAP antibodies was elaborated. Standardization of the immunoenzyme system was shown in tests for specificity, accuracy, and reproducibility.

Animals↗
PubMed2001

Immunochemical assay of glia-specific antigens as a criterion for blood-brain barrier permeability in rats during acute intoxication with sodium barbital.

Enzyme immunoassay showed penetration of two glia-specific antigens, glial fibrillar acid protein GFAP and specific brain glycoprotein alpha(2)GP, through the blood-brain barrier in rats treated with toxic doses of sodium barbital. The permeability of the blood-brain barrier was completely normalized 3 days after treatment. This method can be used in clinical practice for evaluation of the severity of impairment and dynamics of normalization of blood-brain barrier properties during acute intoxication with barbiturates.

Animals↗
PubMed2001

[Permeability of hemato-encephalic barrier in Alzheimer's disease and parkinsonism with cognitive disorders].

The study was made of 17 patients with expected Alzheimer's disease (AD), 29 patients with Parkinson's disease (PD) and 7 with a expected dementia with Levy bodies (DLB). The severity of cognitive disorders was determined according to the following scales: Global Deterioration Rating Scale, Mini-mental State Examination, Mattis Dementia Rating Scale. Besides, the patients state was evaluated, in the whole, according to some scales. Permeability of hemato-encephalic barrier was evaluated according to the blood serum levels of 3 neurospecific proteins--neuron specific enolase, glial fibrillary protein and alpha-glycoprotein. Their determination was performed by ELISA method. The significant elevation of the levels of the proteins studied was found already on the early stages of the disease. Their levels were higher in the patients with the dementia as compared with the individuals without it. There were no differences in cortical, subcortical and combined types of dementia. The authors believe, that some of the proteins studied (neuron specific enolase, for example) may serve as non specific markers of cerebral degeneration.

Alzheimer Disease↗