Comparative Analysis of the Effects of Upconversion Nanoparticles on Normal and Tumor Brain Cells.

Glioma is the most aggressive type of brain tumors encountered in medical practice. The high frequency of diagnosed cases and risk of metastasis, the low efficiency of traditional therapy, and the usually unfavorable prognosis for patients dictate the need to develop alternative or combined approaches for an early diagnosis and treatment of this pathology. High expectations are placed on the use of upconversion nanoparticles (UCNPs). In this study, we have produced and characterized UCNPs doped with the rare-earth elements ytterbium and thulium. Our UCNPs had photoluminescence emission maxima in the visible and infrared spectral regions, which allow for deep optical imaging of tumor cells in the brain. Moreover, we evaluated the toxicity effects of our UCNPs on a normal brain and glioma cells. It was revealed that our UCNPs are non-toxic to glioma cells but have a moderate cytotoxic effect on primary neuronal cultures at high concentrations, a condition that is characterized by a decreased cellular viability and changes in the functional metabolic activity of neuron-glial networks. Despite the great potential associated with the use of these UCNPs as fluorescent markers, there is a need for further studies on the rate of the UCNPs accumulation and excretion in normal and tumor brain cells, and the use of their surface modifications in order to reduce their cytotoxic effects.

The Role of Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor in Chronic Fetal Oxygen Deprivation.

The aim of the study was to define the role of brain-derived and glial cell line-derived neurotrophic factors (BDNF and GDNF) in realization of compensative and adaptive mechanisms of a neonatal organism to hypoxia. MATERIALS AND METHODS: The experiments in vivo have been carried out on pregnant C57BL/6 mice (n=36). Chronic hypobaric hypoxia has been modeled in different pregnancy trimesters. On gestation days E19-20, concentration of BDNF and GDNF in the blood of the pregnant females was determined by enzyme immunoassay. Further, the number of neonatal mice, their weight and body length parameters have been assessed.Parturient mothers (n=88) and their newborn babies followed up at the Clinic of Obstetrics and Gynecology of Pavlov University took part in the clinical investigations. Concentration of BDNF, GDNF, neuron-specific enolase (NSE), and hypoxia-inducible factor (HIF-1ß) in the fetal cord blood has been determined by ELISA. The obtained data were retrospectively compared with cardiotocography, dopplerometry, presence of meconium-stained amniotic fluid and the neonate state at birth, assessment according to the Apgar score, and the course of adaptation period. RESULTS: Chronic hypobaric hypoxia in pregnant mice in trimester I and II resulted in the significant decrease of BDNF and GDNF level, decrease in the number of embryos, and in significant changes in weight/height characteristics of the newborn pups.According to the clinical observations, an increased expression of the neurotrophic factors BDNF, GDNF provides protection to a neonate even if hypoxia factors are present and realized. A low content of BDNF and GDNF was observed in the group of infants with a high risk of developing unfavorable hypoxic damaging effects. CONCLUSION: The protective role of BDNF and GDNF in the regulation of fetal homeostasis in chronic hypoxia has been established experimentally and clinically.

Role of Neurotrophic Factors BDNF and GDNF in Nervous System Adaptation to the Influence of Ischemic Factors.

We developed a complex in vitro model of ischemic damage. Analysis of hippocampal cell viability in primary cultures after modeling of various stress factors revealed the features of action of the main pathological factors of ischemia. Neurotrophic factors BDNF and GDNF produced pronounced neuroprotective effect during modeling both the complex ischemic damage and its individual pathophysiological components. Neurotrophic factor GDNF produced the most pronounced protective effect.

Antioxidant Properties of Glial Cell-Derived Neurotrophic Factor (GDNF).

We propose an in vitro model of chronic oxidative stress based on the use of glucose oxidase. Oxidative stress modeling leads to a significant increase in the number of dead cells in culture. It was shown that the glial cell-derived neurotrophic factor exhibits a pronounced anti-oxidant effect. Preventive application of 1 ng/ml glial cell-derived neurotrophic factor significantly reduced the percentage of dead cells in culture.

[Osteoprotegerin is a new marker of cardiovascular diseases]. / Osteoprotegerin - novyi marker serdechno-sosudistykh zabolevanii.

Osteoprotegerin (OPG) is a glycoprotein that is a representative of the tumor necrosis factor-α receptor superfamily. Information about the possible role of OPG in the development of cardiovascular diseases has begun to appear in the literature in recent years. This review discusses the role of increasing the level of OPG in the development and progression of atherosclerosis and as a consequence of coronary heart disease and chronic heart failure.

Formation of Neural Networks in 3D Scaffolds Fabricated by Means of Laser Microstereolithography.

We developed and tested new 3D scaffolds for neurotransplantation. Scaffolds of predetermined architectonic were prepared using microstereolithography technique. Scaffolds were highly biocompatible with the nervous tissue cells. In vitro studies showed that the material of fabricated scaffolds is not toxic for dissociated brain cells and promotes the formation of functional neural networks in the matrix. These results demonstrate the possibility of fabrication of tissue-engineering constructs for neurotransplantation based on created scaffolds.

Antihypoxic and Neuroprotective Effects of Glial Cell-Derived Neurotrophic Factor (GDNF) in Cultures of Dissociated Hippocampal Cells under Conditions of Experimental Hypoxia.

We analyzed the effect of glial cell derived neurotrophic factor (GDNF) on changes in functional bioelectric and calcium activity in dissociated hippocampal cell cultures under conditions of modeled acute normobaric hypoxia in vitro. GDNF (1 ng/ml) partially neutralized the negative effects of hypoxia on cell survival and parameters of functional network activity. GDNF exhibited a pronounced anti-hypoxic effect.

[Compatibility of cells of the nervous system with structured biodegradable chitosan-based hydrogel matrices].

Hydrogel matrices for cell cultivation have been generated by two-photon laser polymerization of unsaturated chitosan derivatives and methacrylated hyaluronic acid. The adhesive and toxic properties of the matrices have been assessed, and the matrices have been shown to have a good compatibility with primary hippocampal cell cultures. The formation of morphologically normal neural networks by cells of the nervous system cultured on the surface of hydrogel matrices has been observed. The metabolic status of dissociated hippocampal cells cultured on the matrices was similar to that of the control cultures, as shown by the results of MTT reductase activity assay. Thus, matrices based on unsaturated polysaccharide derivatives crosslinked by laser irradiation showed good compatibility with differentiated cells of the nervous system and considerable potential for use in neurotransplantation.

Effect of N-arachidonoyl dopamine on activity of neuronal network in primary hippocampus culture upon hypoxia modelling.

We studied the effect of endocannabinoid N-arachidonoyl dopamine on spontaneous bioelectric activity of cultured hippocampal neurons in a model of hypoxia/reoxygenation. Incubation under hypoxic conditions induced irreversible decrease in spontaneous bioelectric activity of neurons and their death. Application of N-arachidonoyl dopamine during hypoxia and in the post-hypoxic period preserved bioelectric activity and viability of neurons. The protective effect of N-arachidonoyl dopamine was primarily mediated by type I cannabinoid receptors.