Effects of low frequency magnetic stimulation on myelin and inflammation in demyelinated mice / 中华物理医学与康复杂志

Objective:To explore the effect of low frequency magnetic stimulation on myelin and inflammation in the callosum of demyelinated mice.Methods:Thirty-six 6 to 8-week-old male C57BL/6J mice were randomly divided into a control group, a cuprizone (CPZ) group and a magnetic therapy group. The CPZ group and the magnetic therapy group had demyelination induced by feeding a mixed diet containing 0.3% CPZ for 6 weeks, while the control group was given conventional food. The magnetic therapy group was given 50Hz 10mT magnetic stimulation during the 6 weeks for 20min daily, 5 days a week. The body mass of each mouse was observed every 7 days. At the end of the 6th week elevated cross maze experiments were conducted to observe any anxiety state. The myelin sheath in the corpus callosum was observed using Luxol fast blue staining and myelin basic protein (MBP) immunohistochemistry Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the corpus callosum were detected using enzyme-linked immunosorbent assays.Results:After the 6 weeks of treatment, the average body mass of the mice in the magnetic therapy group had improved significantly compared with the CPZ group. The CPZ group′s times in the elevated cross maze experiments were significantly shorter than those of the control group and also shorter than those of the magnetic therapy group. The Luxol staining showed significant myelin loss in the corpus callosum of the CPZ group, but compared with the CPZ group the average loss of myelin in the magnetic therapy group was significantly less. This was further confirmed by the MBP immunohistochemistry. Compared with the control group, the average expression of MBP in the CPZ group was significantly reduced, while in the magnetic therapy group it was significantly increased. Compared with the control group, the average TNF-α and IL-1β levels in the corpus callosum of the CPZ group increased significantly, but compared with the CPZ group the average levels in the magnetic therapy group had decreased significantly.Conclusions:Low frequency magnetic stimulation improves the body weight and anxiety state of mice. That is probably related to less myelin loss and inhibited inflammatory response in the corpus callosum.

Repair effect of cannabinoid on myelin sheath of demyelination model mice induced by cuprizone / 吉林大学学报(医学版)

Objective: To investigate the repair effect of cannabinoid (WIN55212-2) on the myelin sheath of the demyelination model mice induced by cuprizone, and to elucidate its possible mechanism. Methods: A total of 95 C57BL/6 mice were randomly divided into blank control group, model group (0.2% cuprizone for 6 weeks), DMSO group (intraperitoneally injected with the same amount of DMSO mixture from the 3rd week of feeding 0.2% cuprizone) and treatment group (intraperitoneally injected with 1 mg · kg-1 WIN55212-2 from the 3rd week of feeding 0.2% cuprizone). The myelin sheath tissue of the mice was stained by Black-gold II staining technique, and its histomorphology was observed. The expression levels of juxtanodin (JN), myelin basic protein (MBP) and Nkx2. 2 proteins in mouse brain tissue were detected by Western blotting method. Results: The results of Black-gold I staining showed that the corpus callosum of the brain of the mice in blank control group had significant coloration, while the corpus callosum of the mice in model group showed less coloration. Compared with blank control group, the expression levels of JN and MBP proteins in brain tissue of the mice in model group were significantly decreased (P<0.05). Compared with model group and DMSO group, the expression level of JN and Nkx2. 2 proteins in brain tissue of the mice in treatment group were significantly increased (P

Ameliorative effects of Moringa on cuprizone-induced memory decline in rat model of multiple sclerosis / 대한해부학회지

Cuprizone is a neurotoxin with copper-chelating ability used in animal model of multiple sclerosis in which oxidative stress has been documented as one of the cascade in the pathogenesis. Moringa oleifera is a phytomedicinal plant with antioxidant and neuroprotective properties. This study aimed at evaluating the ameliorative capability of M. oleifera in cuprizone-induced behavioral and histopathological alterations in the prefrontal cortex and hippocampus of Wistar rats. Four groups of rats were treated with normal saline, cuprizone, M. oleifera and a combination of M. oleifera and cuprizone, for five weeks. The rats were subjected to Morris water maze and Y-maze to assess long and short-term memory respectively. The animals were sacrificed, and brain tissues were removed for histochemical and enzyme lysate immunosorbent assay for catalase, superoxide dismutase, and nitric oxide. Cuprizone significantly induced oxidative and nitrosative stress coupled with memory decline and cortico-hippocampal neuronal deficits; however, administration of M. oleifera significantly reversed the neuropathological deficits induced by cuprizone.

Kolaviron Protects the Prefrontal Cortex and Hippocampus against Histomorphological and Neurobehavioural Changes in Cuprizone Model of Multiple Sclerosis

Background: This study explored the efficacy of kolaviron—a biflavonoid complex isolatedfrom the seeds of Garcinia kola—in protecting against cuprizone (CPZ)-induced demyelination inboth the prefrontal cortex and the hippocampus of Wistar rats.Methodology: Thirty rats were treated to receive 0.5 mL phosphate-buffered saline (groupA, control), 0.5 mL corn oil (group B), 0.2% CPZ (group C), for 6 weeks, 0.2% CPZ for 3 weeks andthen 200 mg/kg of Kv for 3 weeks (group D), or 200 mg/kg of Kv for 3 weeks followed by 0.2%CPZ for 3 weeks (group E). Rats were assessed for exploratory functions and anxiety-like behaviourbefore being euthanised and perfused transcardially with 4% paraformaldehyde. Prefrontal andhippocampal thin sections were stained in hematoxylin and eosin and cresyl fast violet stains.Results: CPZ-induced demyelination resulted in behavioural impairment as seen byreduced exploratory activities, rearing behaviour, stretch attend posture, center square entry,and anxiogenic characteristics. Degenerative changes including pyknosis, karyorrhexis, neuronalhypertrophy, and reduced Nissl integrity were also seen. Animals treated with Kv showedsignificant improvement in behavioural outcomes and a comparatively normal cytoarchitecturalprofile.Conclusion: Kv provides protective roles against CPZ-induced neurotoxicity throughprevention of ribosomal protein degradation.

Dichotomous roles of microglia in cuprizone-induced demyelination in animal models of multiple sclerosis / 中国比较医学杂志

Microglia are the inherent macrophages and immune surveillance cells in the central nervous system (CNS) and compose the first guard of immune defense in CNS .The activation of microglia is one of the pathological features of many CNS diseases and acts as an important role during the multiple sclerosis (MS) process.MS is a CNS disease characterized by neuroinflammatory infiltration , demyelination and axonal damage.Accumulation of activated microglia at the injury site has been observed in brains of MS patients and experimental animals with complicated mechanisms.Microglia have both detrimental and beneficial roles .For instance, microglia have been shown to recruit and reactivate T cells in the CNS and release many detrimental molecules such as proteases , inflammatory cytokines, and free radicals.Conversely, they have also been observed to aid in axonal regeneration and remyelination as well as assist in the clearance of inhibitory myelin debris .In addition, microglia have been shown to release a variety of neurotrophic factors . Cuprizone [oxalic acid bis (cyclohexylidene hydrazide )] is a well-known copper-chelating agent.Cuprizone ingestion in mice induces a highly reproducible demyelination of distinct brain regions .Discussion on the detrimental and beneficial aspects of microglia in cuprizone animal models will serve to better understand the development of MS and find out new therapeutic targets.This review will further our understanding of the dichotomous roles of microglia in cuprizone -induced demyelination in animal models of multiple sclerosis .

Expression pattern of transcription factor Olig2 in cuprizone-induced mouse model of acute demyelination / 中国实验动物学报

Objective To investigate the expression pattern of transcription factor Olig 2 in cuprizone-induced mouse model of acute demyelination .Methods C57BL/6 mice were fed with 0.2%cuprizone to induce acute demyelina-tion.Immunofluorescence and qRT-PCR were used, and Olig2, MBP and GFAP were detected in the brain tissues of con-trol group and cuprizone-treated groups for 6 weeks and recovery for 2 weeks.Results Severe demyelination occurred in the corpus callosum following 6-weeks exposure to cuprizone , while remyelination was detected in the white matter after the mice were given diet without cuprizone .In the normal mice , Olig2 was expressed in a low level , while the experessions of Olig2 and GFAP were significantly increased , and Olig2 +/GFAP+cells were detected after demyelination .But the expres-sion of MBP was below the normal level with demyelination .After recovery for 2 weeks, the experession of Olig2 was lower, but the experessions of MBP and GFAP were increased .Conclusions Olig2 may play an important role in the glial differ-entiation from neural progenitor cells into active astrocytes , and in the glial scar formation .