Mouse model, multiple sclerosis

Similarly, under certain disease conditions, altered NA innervation and/or AR signaling capacity impairs sympathetic communication with cells of the immune system, influencing disease progression. Altered catecholamine communication with the immune system is evident in autoimmune diseases such as arthritis and multiple sclerosis [5-7] and in infectious diseases, such as leprosy and a mouse model of acquired immunodeficiency syndrome [15, 43, 44], The impact of altered NA innervation of... 

A group from La Jolla Pharmaceuticals has released data on their novel hydrazines in recent scientific [20,59,60] and patent literature [61,62], A series of arylallyl hydrazines (e.g., 8 and 9) were shown to be potent, irreversible inhibitors of rat and human SSAO/VAP-1 [59]. LJP-1207 (8, IC50 = 2nM, human) was evaluated in a series of in vivo inflammation models. Significant efficacy was observed in a mouse ulcerative colitis, mouse LPS-induced septic shock, and the rat carrageenan foot models [20], in a mouse model that resembles human multiple sclerosis [63], and in a transient forebrain ischemia model in estrogen-treated ovariectomized female rats [60]. 

The intramuscular injection of naked pDNA has also been evaluated for therapy of EAE, a mouse model of multiple sclerosis. The disease is induced in mice by s.c. injection of myelin basic protein (MBP) or proteolipid protein (PLP). In a recent study, mice were injected i.m. with pDNA encoding either IL-4/IgG or TGF / 48 hours prior to each MBP injection (on days zero and seven) (Piccirillo and Prud -homme, 1999). The disease severity was 70% lower in the IL-4/IgG or TGF / -treated mice and the mean clinical scores were significantly reduced in both groups. In addition, the IL-4 and TGF -treated mice had significantly reduced CNS inflammation, reduced T cell proliferative responses to MBP and low levels of the Th 1 cytokines IL-12 and IFN7. Thus, the pDNA therapy appeared to shift the mice to a Th2 response, which was therapeutic and reduced the severity of the disease. 

Multiple sclerosis (MS) has traditionally been viewed as a disorder in which myelin is the primary target. However, there is recent evidence for abnormal SNS expression in experimental models of demyelination and in MS. Black et al (1999b) studied Na channel expression in the taiep rat, a mutant model in which myelin is initially formed normally, but then lost as a result of an oligodendrocyte abnormality. They observed the abnormal expression of SNS Na channel mRNA and protein in Purkinje cells following loss of myelin. More recently. Black et al (2000) demonstrated that SNS mRNA and protein, which are not detectable in normal Purkinje cells, are expressed within Purkinje cells in a mouse model of MS, chronic relapsing experimental allergic encephalomyelitis. Black et al (2000) have also demonstrated the expression of SNS mRNA (Fig. 7a, b) and protein (Fig. 7e, f) within cerebellar Purkinje cells from tissue obtained post-mortem from MS patients, but not in controls with no neurological disease (Fig. 7c, g). 

In murine models of experimental autoimmune encephalomyelitis (multiple sclerosis), diabetes mellitus type 1, and inflammatory bowel disease, treatment with 1,25-hydroxycholecalciferol (in conjunction with adequate calcium intake) has been shown to inhibit the development of disease (Froicu et al., 2003 Hypponen, 2004 Van Amerongen et al., 2004). In lupus mouse strains, however, a more complex situation is seen, with some evidence of worsening of disease (particularly with respect to measures of renal damage) with 1,25-hydroxycholecalciferol treatment (Vaisberg et al., 2000). 

Simultaneous treatment with CXCLll-based antagonist 49 (for definition see Section 13.3.3) and a CXCR4 antagonist blocked experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Additional investigations revealed that 49 inhibited the effector phase of the immune response, while the CXCR4 antagonist inhibited the sensitization phase [19]. 

It has been well established that a number of chemokines including, KC, IP-10, MIP-1 a, RANTES, MARC (murine MCP-3), and TCA-3 (murine 1-309) are upregulated during the course of murine experimental allergic encephalitis (EAE) a mouse model of multiple sclerosis (MS) (25). Glabinski et al. have also demonstrated that the chemokines... 

Anderson SA, Shukaliak-Quandt 1, Iordan EK et al. Magnetic resonance imaging of labeled T-ceUs in a mouse model of multiple sclerosis. Ann Neurol 2004 55 654-659. 

MnHiple sclerosis Lithium was effective in a mouse model of experimental autoimmune encephalomyelitis (a model of multiple sclerosis). It reduced neurological symptoms if administered both before and after induction of the illness ami the animals rapidly relapsed if lithium was withdrawn [34 ]. 

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