To investigate the effects of the rhLIF recombinant human leukemia inhibitory factor on the structural and functional changes in the central nervous system in the cuprizone-induced experimental model of multiple sclerosis in mice and to evaluate the involvement of the brain macrophages, T-lymphocytes and antioxidant enzymes in the observed rhLIF effects. Methods. Young 129/Sv mice were fed with the cuprizone neurotoxin daily for three weeks. rhLIF was injected daily (50 μg/kg) after seven days of the cuprizone treatment. We used histology, flow cytometry, spectrophotometric and functional methods. Results. The cuprizone treatment resulted in an increase in the number of the brain and spinal cord neurons with destructive changes, the brain macrophages, CD3 +-cells and the content of malondialdehyde; it changes the behavior of animals, decreases the brain superoxide dismutase and glutathione peroxidase activities. The rhLIF injection partially or completely restored the cuprizone-changed parameters. The effect of rhLIF was preserved during two months after the experiment completion. Conclusions. The neuroprotective effect of rhLIF is connected with a decrease in the cuprizone-induced changes in the number of the brain T-cells and macrophages and the activity of antioxidant enzymes.

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Cytokines and growth factors exhibit neurotropic, anti-inflammatory and immunomodulatory properties, and therefore can affect the functioning of the nervous system at demyelinating disorders.Purpose. To identify changes in T-lymphocytes, macrophages, oxidative stress and antioxidant defence factors, endocrine thymus function in the brain and behaviour of mice receiving neurotoxin cuprizone and recombinant human proteins: interleukin-10 (rhIL-10) and fibroblast growth factor (rhFGF-2).Materials and methods. 4-6-month-old 129/Sv mice received cuprizone with food every day for 3 weeks. From the 7th day of cuprizone diet, they received different doses of rhIL-10 and rhFGF-2. The content of СD3+ Т-cells, macrophages, malondialdehyde, activity of antioxidant enzymes in the brain and the level of thymulin in the blood were determined. Behavioural reactions were assessed in the “open field” test.Results. In the brain of mice receiving cuprizone and rhIL-10, there was a decrease in the number of СD3+ Т-cells and the activity of macrophages, which significantly increased under the influence of the toxin. After cytokine injection, the activity of superoxide dismutase, catalase and glutathione peroxidase increased significantly in the brain, as well as the level of thymulin in the blood. Motor, emotional and exploratory activity of mice, significantly suppressed by the cuprizone, was increased after the introduction of rhIL-10. The effect of rhIL-10 on the test parameters is more pronounced at a dose of 5 μg/kg than 50 μg/kg. After injection of rhFGF-2 in the mice with cuprizone diet, there is a decrease in the activity of brain macrophages and an increase of the level of thymulin in the blood depending on the dose of this factor; the motor activity of these animals increased regardless of the rhFGF-2 dose.Conclusion. The injections of rhIL-10 and rhFGF-2 provide dose-dependent positive effects on the pathogenetic factors of experimental demyelinating pathology, as well as the functional state of the nervous system. Whereas, the injections of rhIL-10 have more pronounced effects.

The search for tools that increase the effectiveness of cell therapy of demyelinating pathology is relevant. They may be preparations that affect the pathogenetic factors of this pathology, in particular, the pineal hormone melatonin.The purpose of the work is to evaluate the involvement of immune system and antioxidant defense in the implementation of the protective effects of melatonin on morpho-functional disorders in the central nervous system induced by neurotoxin cuprizone.Materials and methods. The toxic demyelination model was induced on 129/Sv mice at the age of 3-5 months by adding cuprizone to food for 3 weeks. Since the 7th day of cuprizone administration, melatonin was injected intraperitoneally at 18:00 daily, at a dose of 1 mg/kg. In the brain of mice, the proportion of CD3+, Nestin+ cells and phagocytic macrophages, the content of malondialdehyde and the activity of antioxidant enzymes was determined. Blood serum was tested for thymic hormone thymulin levels. In the animals, we evaluated the structure of the brain and spinal cord neurons by Nissl staining of histological sections as well as analyzed behavioural reactions in the "open field" test.Results. In the brain of the mice received cuprizone, the proportion of CD3+ and Nestin+ cells, active macrophages and malondialdehyde content increases, glutathione peroxidase and glutathione reductase levels decreases. In the brain and spinal cord of the mice with a cuprizone diet, the proportion of altered neurons increases, and motor and emotional activity decreases. The introduction of melatonin results in a decrease in the relative number of CD3+ cells, active macrophages and malondialdehyde content, increased activity of glutathione peroxidase, glutathione reductase and level of thymulin. In such mice, the proportion of unchanged neurons increases as the number of Nestin+ cells decreases and behavioural responses are also improved.Conclusions. The neuroprotective effect of melatonin in demyelinating pathology is realized through the factors of the immune system and oxidative stress. The results may be useful in the development of new biotechnological approaches to the treatment of demyelinating pathology, in particular, multiple sclerosis.

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