EFFECT OF INVESTIGATIONAL COMBINATIONS OF NEUROPROTECTANTS ON THE LEVEL OF S 100 AND NSE PROTEIN IN THE BLOOD SERUM OF PATIENTS WITH MODERATE AND SEVERE ISCHEMIC STROKE.

Ischemic cerebral stroke (ICS) is a devastating neurological pathology associated with enormous comorbidity and mortality. Preliminary experimental screening of cerebroprotective agents with different mechanisms of action was performed: Edaravone, Cerebrolysin, Choline alfoscerate, Citicoline, Mexidol, the most effective combinations of cerebroprotectors were identified, followed by their screening for efficacy in clinical conditions by neuron-specific enolase (NSE) and S100 protein, as one of the main biochemical markers of brain damage in acute ischemic stroke. Different combinations of neuroprotectants identified as the most effective in experimental screening differed in their ability to correct serum levels of S100 and NSE protein in ischemic stroke in clinical settings. The lowest effectiveness in the correction of neuroglioproliferative processes was recorded when using only conventional therapy (CT), which was determined according to the Order of the Ministry of Health of Ukraine of 03.08.2012 №602, without the use of neuroprotectors. Whereas, the use of a neuroprotective combination/complex (NPC) (cerebrolysin+citicoline) in the treatment of ischemic strokes in terms of the effectiveness of correction of neuroglioproliferative processes was 1,7-2,7 times (p<0.01) higher than conventional therapy, and 1,2-1,4 times (p<0.05) higher than treatment that included the use of a neuroprotective combination - cerebrolysin+mexidol.

THE EFFECT OF ADEMOL ON THE DNA FRAGMENTATION OF CEREBRAL CORTEX CELLS IN RATS WITH EXPERIMENTAL TRAUMATIC BRAIN INJURY.

THE AIM OF THE STUDY: To determine the effect of Ademol on the deoxyribonucleic acid (DNA) fragmentation of the cerebral cortex cells (apoptosis) of rats with traumatic brain injury (TBI). MATERIALS AND METHODS: An experimental model of severe trauma was created in male rats using an air pistol. The therapeutic effect of Ademol in TBI was evaluated at a dose of 2 mg/kg intravenously at intervals of 2 t/d for 8 days. As a drug for the control group we used 0.9% NaCl at a dose of 2 ml/kg, and as a comparison drug - amantadine sulfate at a dose of 5 mg/kg. On day 8 after TBI and decapitation of animals, the parts of the cerebral cortex were taken to assess further DNA fragmentation in cells by the flow cytometry method. RESULTS AND CONCLUSIONS: The post-traumatic period of model TBI in rats is accompanied by a probable increase in the level of DNA fragmentation in the nucleus of cerebral cortex cells on the 8th day of the experiment. By the antiapoptotic effect in conditions of post-traumatic brain injury, Ademol solution therapy was significantly better than the infusion of 0.9% NaCl and amantadine sulfate at an average of 46.2 and 27.2%, respectively (p<0.05).

EVALUATION OF THE EFFECT OF ADEMOL ON THE DYNAMICS OF NEURON-SPECIFIC ENOLASE IN TRAUMATIC BRAIN INJURY IN RATS.

The great hopes of modern medicine for neuroprotective therapy have stimulated scientists around the world to actively search for new effective means of influencing the pathophysiological cascades of the development of neuronal damage. Aim. To evaluate the effect of the use of the adamantane derivative 1-adamantylethyloxa-3-morpholino-2-propanol hydrochloride (ademol) compared with amantadine sulfate and 0.9% NaCl solution on the activity dynamics of neuron-specific enolase in rats with acute traumatic brain injury (TBI) . The therapeutic effect of ademol in experimental traumatic brain injury was evaluated using a dose of 2 mg/kg (i/v) every 12 hours for 8 days. The pseudo-operated animals and the control group received a 0.9% NaCl solution at a dose of 2 ml/kg i/v, and the comparison group received amantadine sulfate at a dose of 5 mg/kg in the same mode. To determine the effectiveness of the studied drugs in brain injury, the level of neuron-specific enolase (NSE) was used. The course infusion in rats with TBI of solutions of ademol (2 mg/kg) and amantadine sulfate (5 mg/kg) during the 8 days of the TBI model, significantly reduced the increase in the NSE level in animals of the control pathology group by an average of 52.1 and 38.2%. Thus, the results obtained indicate that when using ademol at a dose of 2 mg/kg i/v and amantadine sulfate (5 mg/kg i/v), powerful neurocytoprotective properties appear against the background of a model head injury. Moreover, the neuroprotective effect of ademol manifested itself more clearly, since in terms of the ability to prevent the increase in NSE levels, it significantly dominated the reference drug by an average of 22.5%.

First experience of hematopoietic stem cell transplantation treatment of Shwachman-Diamond syndrome using unaffected HLA-matched sibling donor produced through preimplantation HLA typing.

The only proven cure for Shwachman-Diamond syndrome (SDS) bone marrow failure is allogeneic hematopoietic stem cell transplantation (HSCT). However HSCT with donors other than HLA-identical siblings is associated with high mortality and unfavorable prognosis. This paper presents the first experience of HSCT treatment of SDS using an unaffected HLA-identical sibling produced through preimplantation genetic diagnosis (PGD). The patient was a 6-year-old blood transfusion-dependent SDS baby girl with secondary myelodysplastic syndrome, for whom no HLA-identical donor was available. As a result of PGD, two unaffected HLA matched embryos were identified; one of them was randomly selected for transfer, resulting in a clinical pregnancy and birth of an apparently healthy child. The patient underwent allogeneic transplantation of cord blood hematopoietic stem cells, together with bone marrow from this sibling, resulting in complete hemopoietic recovery. The patient was no longer transfusion-dependent and had normal blood values 160 days after transplantation.

Investigation of the mechanism of action of atmospheric pollutants on the central nervous system and comparative evaluation of methods of study.

Some aspects of the mechanism of action of atmospheric pollutants (acetone, benzene, ammonia, formaldehyde, and ozone) on the central nervous system were studied by using methods of functional electroencephalography (analysis of the readjustment reaction to a rhythmic light stimulus, evoked potentials of the cerebral cortex, and determination of the photometrazol thresholds). Effects of the compounds were determined for the various structures of the cerebral cortex of experimental animals. The most sensitive structures were those which were first to associate in the reaction to toxic agents (the corticomedial nucleus of the amygdaloid complex and the olfactory bulb). EEG indices were observed which were indicative of an adverse effect (epileptoid activity in the most sensitive formations of the brain and a stable generalized stress rhythm in the neocortex and in the limbic ascending reticular system). During long-term action of toxic materials at low concentrations, changes were observed in the parameters of the primary and secondary responses of the visual evoked potential which were indicative of a disturbance of the cortical inhibition processes. This can be considered one effect of atmospheric pollutants at low concentrations. Problems of the comparative sensitivity of the various methods of studying the central nervous system are being investigated with a single compound: carbon bisulfide. In human experiments concerned with the fine coordination of measured movements such as writing and the solution of arithmetic problems, the subject-operator observed that repeated inhalation of subsensory concentrations of carbon bisulfide (0.08 mg/m3 level) disturbs the rate of execution of assigned motor processes. In tests with rats with developed instrument conditioned reflexes, it was shown that entire behavioral acts deteriorate under the effect of the same carbon bisulfide concentration. In tests on rabbits, simultaneous neurophysiological and neurochemical analyses were performed on the changes in the functional state of the central nervous system under chronic exposure to carbon bisulfide at various concentrations.