Neuroprotective effect of the recombinant human leukemia inhibitory factor in mice with an experimental cuprizone model of multiple sclerosis: possible mechanisms

Abstract

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.

The effects of combined administration of human umbilical cord-derived multipotent mesenchymal stromal cells and melatonin or fibroblast growth factor-2 to aged mice with a toxic cuprizone model of demyelination

“…Positive changes in the behavior of mice with a cuprizone diet after the transplantation of UC-MMSCs can most likely be associated with their anti-inflammatory properties, in particular, the synthesis of IL-10, a decrease in the manifestation of active gliosis in the brain [25,31]. According to our data, in mice with a cuprizone diet, the number of active macrophages in the brain decreases under the influence of cytokines with an anti-inflammatory effect [28].…”

“…UC-MMSCs of the 2 nd passage were injected once into the tail vein on the 10 th day of the cuprizone diet at a dose of 5•10 5 cells per 50 μL in saline. It was found that after 8-10 days of cuprizone diet in the brain of mice of different lines, including 129/Sv, there was oligodendrocyte apoptosis and changes in the structure of neurons and behavior [24,28]. In addition, the therapeutic effect of human bone marrow-derived MMSCs after transplantation into mice taking cuprizone has been shown [29].…”

Melatonin and fibroblast growth factor-2 potentiate the effects of human umbilical cord multipotent mesenchymal stromal cells in mice with cuprizone-induced demyelination

“…hMMSCs were injected once into the tail vein of mice on the 10th day of cuprizone diet at a dose of 5•10 5 cells per 50 μl of saline. It was found that after 8-10 days of cuprizone treatment there were signs of demyelination and apoptosis of oligodendrocytes in the brain as well as changes in the structure of neurons and in the behavior of mice [1,20].…”

“…Factors of oxidative stress and antioxidant protection were determined, as described previously [12,20]. The malondialdehyde (MDA) content in brain homogenate was determined by colour intensity of the trimethine complex formed between thiobarbituric acid and MDA.…”

Вплив Інтерлейкіну-10 На Фактори Імунної Системи Й Антиоксидантного Захисту Головного Мозку, Функцію Тимуса І Поведінку У Мишей Із Токсичною Купризоновою Моделлю Демієлінізації

“…При этом мы не исключаем возможности получения отдаленного нейропротекторного эффекта rhIL-10 в дозе 5 мкг/кг у мышей с купризоновой моделью демиелинизации. Подобный эффект у мышей с этой моделью мы уже наблюдали у цитокина с нейротропными свойствами -лейкемия ингибиторного фактора [31].…”