Toxin-Based Models to Investigate Demyelination and Remyelination.

Clinical myelin diseases, and our best experimental approximations, are complex entities in which demyelination and remyelination proceed unpredictably and concurrently. These features can make it difficult to identify mechanistic details. Toxin-based models offer lesions with predictable spatiotemporal patterns and relatively discrete phases of damage and repair: a simpler system to study the relevant biology and how this can be manipulated. Here, we discuss the most widely used toxin-based models, with a focus on lysolecithin, ethidium bromide, and cuprizone. This includes an overview of their respective mechanisms, strengths, and limitations and step-by-step protocols for their use

Co-Administration of Vitamins E and D3 on Spatial Learning and Memory of Hippocampal Formation of Rat Following Ethidium Bromide- Induced Demyelination

Background: The hippocampus as part of the limbic system has a major role in the formation of several types of memory including spatial memory. Cognitive and memory impairment have been reported in patients with multiple sclerosis (MS) by several studies and vitamins have antioxidant role for neuro-regeneration. The present study investigates the effects of combined administration of vitamins E and D3 on spatial learning and memory in the demyelinated hippocampus of rat following administration of ethidium bromide. Materials and Methods: Male Wistar rats were anesthetized with intraperitoneal injection of chlorate hydrate. The animal head was fixed in a stereotaxic apparatus and 3 microliter of ethidium bromide was injected into the dentate gyrus of hippocampus for 7 days. Behavioral tests after intra-peritoneal administration of vitamin E (mg/kg100) and D3 (μg/kg5) were carried out. Animals were subjected to 5 days of training in the Morris water maze 4 days with the invisible platform to test spatial learning and the 5th day with the visible platform to test sensory-motor coordination. Results: The results showed that co-administration of vitamins E and D3 significantly decreased the total traveled distance to the platform compared to the lesion group. However, the indexes of escape latency and swimming speed did not decrease significantly. Conclusion: The co-administration of vitamins E and D3 slightly enhanced spatial learning and memory impairment probably through its neuro-protective effect in the hypocampus

Probiotics Lactobacillus plantarum and Bifidobacterium B94: Cognitive function in demyelinated model

Background: Multiple Sclerosis (MS) is a disease of the immune system that creates damage of Learning and memory in that. Using probiotic supplements is recommended for preventing MS disease and improving memory. This study aimed to investigate the effect of Lactobacillus Plantarum (LP) and bifidobacterium B94 (BB94), on acquisition phase of spatial memory in the local demyelination of rats' hippocampus. Methods: In this study, 32 male Wistar rats were divided into control, damage group and treatment groups. Treatment groups were including (LP) and (BB94). After the induction of demyelination by 3 μl of EB into the right dentate gyrus of the hippocampus in treatment groups, 1.5�108 probiotic bacteria were administered by gavage for 28 days. Data was analyzed using one-way ANOVA and Tukey post-hoc tests (p=0.05). Results: Findings demonstrated that injection of EB caused a significant increase in traveled distance (p < 0.01) and also escape latency (p < 0.05) compared with control group. Also, effect administrations of (LP) and (BB94) on traveled distance and escape latency were reviewed, and it was determined that administration of them do not cause significant reduction in the traveled distance compared with the lesion group. Also mentioned probiotics has no significant effect on swimming speed compared with lesion and saline groups. Conclusion: According to some studies, probiotics have a positive impact on improving the performance of spatial memory and learning, although the results of the current study could not indicate finality of this assumption . It seems that more researches is needed on this subject

The Relationship between Level of Vitamin C in Follicular Fluid and ‎Maturation of Oocytes and Embryo Quality in Patients Undergoing In-vitro ‎Fertilization

BACKGROUND AND OBJECTIVE: Oxidative stress and its adverse effects in vitro or on the body can reduce the number of reproductive cells and embryo quality. Given the fact that vitamin C is a natural antioxidant with a protective role, in this study we aimed to evaluate the relationship between the level of vitamin C in follicular fluid (FF) and maturation of oocytes and embryo quality of patients undergoing in vitro fertilization (IVF). METHODS: This cross-sectional study was performed on the eggs and embryos of 50 patients admitted to IVF unit of Al Zahra Hospital, Rasht, Iran. Patients underwent the same mediations used to induce ovulation, and then they were injected 10000 units of human chorionic gonadotropin. Finally, they underwent 36 hours of follicle suction. Vitamin C level in FF was measured by biochemical methods. Maturation of oocytes and embryo quality were examined with inverted light microscope. FINDINGS: After examining 583 eggs and 275 embryos the following results were obtained: the percentage of metaphase II oocytes in vitamin C level of less than one was 81.3% (412), but when compared to vitamin C level of one or more, it was 71.1% (54), which were significantly different (p=0.038). In the sub-classification, vitamin C level (0.5-1 mg/dl), MII oocyte frequency and the two pronuclei embryos were higher but the difference was not statistically significant. CONCLUSION: The results showed that the quality of oocyte maturation and embryos in lower levels of vitamin C levels had improved, as compared to higher levels

Anti-inflammatory effect of KW-2449 on autoimmune encephalomyelitis: An experimental study on mice

Background: The KW-2449 is a novel multikinase inhibitor that inhibits FLT3, ABL, ABL-T315I, and Aurora A. FLT3 and Aurora A kinases play an important role in the pathogenesis of multiple sclerosis (MS). KW-2449 could modulate immune cells, but the immunomodulatory effects of KW-2449 on experimental autoimmune encephalomyelitis (EAE) have not been investigated yet. The aim of the present study is to investigate the effects of KW-2449 on EAE mouse model. Methods: In this study, C57BL/6 EAE mice were orally treated with (10 mg/kg/day) KW-2449 solution and compared with EAE and control mice. Following the treatment, histological analyses were performed on the brain and cerebellum to evaluate the pathological score. The gene expression levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) were measured using qRT-PCR. The serum levels of TNF-α, IL-6, CCL-2 and MMP-2 were determined by using quantitative enzyme-linked immunosorbent assay (ELISA). Results: The results indicated that the clinical score, the infiltration of inflammatory cells and the demyelination in EAE mice treated with KW-2449 decreased significantly compared to control groups. KW-2449 also decreased TNF-α, IL-6, CCL-2 inflammatory cytokines, and MMP-2 in both brain mRNA expressions and serum levels of EAE mice. Conclusion: The KW-2449, aging as a multi-kinase inhibitor, modulates the inflammatory responses of cytokine cascades either in the brain or in plasma and reduces EAE pathogenesis manifestation

Anti-inflammatory effect of KW-2449 on autoimmune encephalomyelitis: An experimental study on mice

Background: The KW-2449 is a novel multikinase inhibitor that inhibits FLT3, ABL, ABL-T315I, and Aurora A. FLT3 and Aurora A kinases play an important role in the pathogenesis of multiple sclerosis (MS). KW-2449 could modulate immune cells, but the immunomodulatory effects of KW-2449 on experimental autoimmune encephalomyelitis (EAE) have not been investigated yet. The aim of the present study is to investigate the effects of KW-2449 on EAE mouse model. Methods: In this study, C57BL/6 EAE mice were orally treated with (10 mg/kg/day) KW-2449 solution and compared with EAE and control mice. Following the treatment, histological analyses were performed on the brain and cerebellum to evaluate the pathological score. The gene expression levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) were measured using qRT-PCR. The serum levels of TNF-α, IL-6, CCL-2 and MMP-2 were determined by using quantitative enzyme-linked immunosorbent assay (ELISA). Results: The results indicated that the clinical score, the infiltration of inflammatory cells and the demyelination in EAE mice treated with KW-2449 decreased significantly compared to control groups. KW-2449 also decreased TNF-α, IL-6, CCL-2 inflammatory cytokines, and MMP-2 in both brain mRNA expressions and serum levels of EAE mice. Conclusion: The KW-2449, aging as a multi-kinase inhibitor, modulates the inflammatory responses of cytokine cascades either in the brain or in plasma and reduces EAE pathogenesis manifestation. © 2021 Bentham Science Publishers

The effects of D-aspartate on neurosteroids, neurosteroid receptors, and inflammatory mediators in experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a widely used model for multiple sclerosis. The present study has been designed to compare the efficiencies of oral and intraperitoneal (IP) administration of D-aspartate (D-Asp) on the onset and severity of EAE, the production of neurosteroids, and the expression of neurosteroid receptors and inflammatory mediators in brain of EAE mice.Objective: Experimental autoimmune encephalomyelitis (EAE) is a widely used model for multiple sclerosis. The present study has been designed to compare the efficiencies of oral and intraperitoneal (IP) administration of D-aspartate (D-Asp) on the onset and severity of EAE, the production of neurosteroids, and the expression of neurosteroid receptors and inflammatory mediators in the brain of EAE mice. Methods: In this study, EAE was induced in C57BL/6 mice treated with D-Asp orally (D-Asp-Oral) or by IP injection (D-Asp-IP). On the 20th day, brains (cerebrums) and cerebellums of mice were evaluated by histological analyses. The brains of mice were analyzed for: 1) Neurosteroid (Progesterone, Testosterone, 17β-estradiol) concentrations; 2) gene expressions of cytokines and neurosteroid receptors by reverse transcription polymerase chain reaction, and 3) quantitative determination of D-Asp using liquid chromatography-tandem mass spectrometry. Further, some inflammatory cytokines and matrix metalloproteinase-2 (MMP-2) were identified in the mouse serum using enzyme-linked immunosorbent assay kits. Results: Our findings demonstrated that after D-Asp was administered, it was taken up and accumulated within the brain. Further, IP injection of D-Asp had more beneficial effects on EAE severity than oral gavage. The concentration of the testosterone and 17β-estradiol in D-Asp-IP group was significantly higher than that of the control group. There were no significant differences in the gene expression of cytokine and neurosteroid receptors between control, D-Asp-IP, and D-Asp-Oral groups. However, IP treatment with D-Asp significantly reduced C-C motif chemokine ligand 2 and MMP-2 serum levels compared to control mice. Conclusion: IP injection of D-Asp had more beneficial effects on EAE severity, neurosteroid induction and reduction of inflammatory mediators than oral gavage