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EAE Mice (eae + mouse)
Selected AbstractsConserved fate and function of ferumoxides-labeled neural precursor cells in vitro and in vivoJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2010Mikhal E. Cohen Abstract Recent progress in cell therapy research for brain diseases has raised the need for non-invasive monitoring of transplanted cells. For therapeutic application in multiple sclerosis, transplanted cells need to be tracked both spatially and temporally, in order to assess their migration and survival in the host tissue. Magnetic resonance imaging (MRI) of superparamagnetic iron oxide-(SPIO)-labeled cells has been widely used for high resolution monitoring of the biodistribution of cells after transplantation into the central nervous system (CNS). Here we labeled mouse glial-committed neural precursor cells (NPCs) with the clinically approved SPIO contrast agent ferumoxides and examined their survival and differentiation in vitro, as well as their functional response to environmental signals present within the inflamed brain of experimental autoimmune encephalomyelitis (EAE) mice in vivo. We show that ferumoxides labeling does not affect NPC survival and pluripotency in vitro. Following intracerebroventricular (ICV) transplantation in EAE mice, ferumoxides-labeled NPCs responded to inflammatory cues in a similar fashion as unlabeled cells. Ferumoxides-labeled NPCs migrated over comparable distances in white matter tracts and differentiated equally into the glial lineages. Furthermore, ferumoxides-labeled NPCs inhibited lymph node cell proliferation in vitro, similarly to non-labeled cells, suggesting a preserved immunomodulatory function. These results demonstrate that ferumoxides-based MRI cell tracking is well suited for non-invasive monitoring of NPC transplantation. © 2009 Wiley-Liss, Inc. [source] Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitisJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2008Jahan Ara Abstract Although spontaneous remyelination occurs in multiple sclerosis (MS), the extent of myelin repair is often inadequate to restore normal function. Oligodendrocyte precursors remaining in nonremyelinating MS plaques may be restricted by an inhibitory signal. Bone morphogenetic proteins (BMPs) have been implicated as repressors of oligodendrocyte development and inducers of astrogliogenesis. We hypothesized that BMPs are up-regulated in MS lesions and play a role in demyelination and astrogliosis. We examined expression of BMPs in an animal model of MS, chronic experimental autoimmune encephalomyelitis (EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide in C57BL/6 mice. By 14 days postimmunization, compared to those of control mice, the lumbar spinal cords of MOG-peptide EAE mice demonstrated prominent astrogliosis, infiltration of inflammatory cells, and disrupted expression of myelin proteins. Quantitative RT-PCR showed that expression of BMP4, BMP6, and BMP7 mRNA increased 2- to 4-fold in the lumbar spinal cords of animals with symptomatic EAE versus in vehicle-treated and untreated controls on days 14, 21, and 42 postimmunization. BMP2 mRNA expression was not altered. BMP4 mRNA was much more abundant in the spinal cords of all animals than was mRNA encoding BMP2, BMP6, and BMP7. Immunoblot analysis confirmed the increased expression of BMP4 in the EAE animals. Immunohistochemistry revealed increased BMP4 immunoreactivity in areas of inflammation in MOG-peptide EAE animals. BMP4 labeling was mostly limited to macrophages but was sometimes associated with astrocytes and oligodendrocytes. These results indicate that members of the BMP family are differentially expressed in adult spinal cord and are up-regulated during EAE. © 2007 Wiley-Liss, Inc. [source] An Iranian herbal-marine medicine, MS14, ameliorates experimental allergic encephalomyelitisPHYTOTHERAPY RESEARCH, Issue 8 2008Azita Parvaneh Tafreshi Abstract Multiple sclerosis is an inflammatory and demyelinating disease of the central nervous system which mainly affects young adults. To overcome wide spectrum troublesome symptoms of multiple sclerosis which affects the quality of life both in patients and their families, new drugs and remedies have been examined and offered. The preclinical beneficial effects of different medicines have mostly been examined in an animal model of multiple sclerosis called experimental allergic encephalomyelitis (EAE). In this study we have tested a traditionally used natural (herbal-marine) product called MS14 in EAE mice. EAE mice were fed with MS14 containing diet (30%) on the immunization day and monitored for 20 days. The results show that while clinical scores and therefore severity of the disease was progressive in normal-fed EAE mice, the disease was slowed down in MS14 -fed EAE mice. Moreover, while there were moderate to severe neuropathological changes in normal fed mice, milder changes were seen in MS14 fed mice. Copyright © 2008 John Wiley & Sons, Ltd. [source] Preferential recruitment of interferon-,,expressing TH17 cells in multiple sclerosis,ANNALS OF NEUROLOGY, Issue 3 2009Hania Kebir MSc Objective There is substantial evidence supporting the role of interferon (IFN)-,,producing T helper (TH) 1 and interleukin (IL)-17,expressing TH17 lymphocytes in multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). However, to date little is known about the potential cooperative interplay between these 2 cytokines. In the current study, we sought to evaluate the frequency of IFN-,,expressing TH17 lymphocytes in MS and EAE, and study their recruitment into the central nervous system (CNS). Methods Human TH17 lymphocytes were expanded in vitro from the blood of healthy controls and relapsing MS patients using IL-23. Immune cell migration to the CNS was assessed in vitro with primary cultures of human blood,brain barrier (BBB)-derived endothelial cells, and in vivo in EAE mice. Results We demonstrate that in response to IL-23, human memory lymphocytes expand into a TH17 phenotype, with a subpopulation of cells simultaneously expressing IFN-, and IL-17. We note that lymphocytes obtained from the blood of relapsing MS patients have an increased propensity to expand into IFN-,,producing TH17 cells and identify numerous T lymphocytes coexpressing IL-17 and IFN-, in brain tissue of MS patients. We also find lymphocytes expressing both the TH1- and the TH17-associated transcription factors ROR,t and T-bet, in situ and in vitro. We further provide in vitro and in vivo evidence that IFN-,+ TH17 lymphocytes preferentially cross the human BBB and accumulate in the CNS of mice during the effector phase of EAE. Interpretation Our data underscore the involvement of IFN-,+ TH17 lymphocytes in the pathology of MS and EAE and their preferential recruitment into the CNS during inflammatory events. Ann Neurol 2009;66:390,402 [source] Exacerbation of experimental autoimmune encephalomyelitis after withdrawal of phenytoin and carbamazepineANNALS OF NEUROLOGY, Issue 1 2007Joel A. Black PhD Objective In vitro observations and studies in murine experimental autoimmune encephalomyelitis (EAE) have shown protective effects of sodium channel blockers on central nervous system axons and improved clinical status when treatment is continued throughout the period of observation. Several clinical studies of sodium channel blockers are under way in patients with multiple sclerosis. Here we asked whether a protective effect would persist after withdrawal of a sodium channel blocker. Methods We studied a mouse model of myelin oligodendrocyte glycoprotein,induced EAE treated with phenytoin or carbamazepine. Results Both phenytoin and carbamazepine significantly improved the clinical course of the disease. Withdrawal of phenytoin resulted in acute exacerbation, accompanied by a significantly increased inflammatory infiltrate within the central nervous system and the death of nearly 60% of EAE mice. There were no clinical worsening or deaths in control mice after withdrawal of phenytoin. Withdrawal of carbamazepine led to acute worsening of EAE symptoms, increased inflammatory infiltrate, and was associated with the death of 8% of mice. Interpretation These results, together with results showing effects of sodium channel blockers in immune cells, raise questions about the long-term effects of sodium channel blockers in neuroinflammatory disorders, and suggest that clinical studies of sodium channel blockers in these disorders should be planned carefully. Ann Neurol 2007 [source] | ||||||||||