Richard Ransohoff

Summary

Affiliation: Cleveland Clinic Foundation
Country: USA

Publications

  1. doi Is microglial apoptosis an early pathogenic change in cerebral X-linked adrenoleukodystrophy?
    Florian S Eichler
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Ann Neurol 63:729-42. 2008
  2. pmc Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation
    Se Hoon Choi
    Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA
    Neuron 59:568-80. 2008
  3. pmc BAFF/APRIL system in pediatric OMS: relation to severity, neuroinflammation, and immunotherapy
    Michael R Pranzatelli
    Department of Neurology, National Pediatric Myoclonus Center and Neuroimmunology Laboratory, and Southern Illinois University School of Medicine, PO Box 19643, Springfield, IL 62794 9643, USA
    J Neuroinflammation 10:10. 2013
  4. pmc IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils
    Carine Savarin
    Department of Neurosciences NC30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Neuroinflammation 9:104. 2012
  5. ncbi The anatomical and cellular basis of immune surveillance in the central nervous system
    Richard M Ransohoff
    Neuroinflammation Research Center and Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Nat Rev Immunol 12:623-35. 2012
  6. doi Animal models of multiple sclerosis: the good, the bad and the bottom line
    Richard M Ransohoff
    Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
    Nat Neurosci 15:1074-7. 2012
  7. pmc Innate immunity in the central nervous system
    Richard M Ransohoff
    Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Clin Invest 122:1164-71. 2012
  8. pmc Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis
    D R Huang
    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
    J Exp Med 193:713-26. 2001
  9. pmc Human cerebrospinal fluid contains CD4+ memory T cells expressing gut- or skin-specific trafficking determinants: relevance for immunotherapy
    Pia Kivisakk
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA
    BMC Immunol 7:14. 2006
  10. ncbi Natalizumab for multiple sclerosis
    Richard M Ransohoff
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute and Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, OH 44195, USA
    N Engl J Med 356:2622-9. 2007

Research Grants

  1. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2001
  2. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2005
  3. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2002
  4. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2004
  5. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2009
  6. Gender differences in immune responses in MS
    Richard Ransohoff; Fiscal Year: 2009
  7. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2006
  8. Chemokine Regulation on Central Nervous System Inflammation in Multiple Sclerosis
    Richard Ransohoff; Fiscal Year: 2007
  9. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2005
  10. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2003

Detail Information

Publications93

  1. doi Is microglial apoptosis an early pathogenic change in cerebral X-linked adrenoleukodystrophy?
    Florian S Eichler
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Ann Neurol 63:729-42. 2008
    ..In humans, the genetic defect causes progressive inflammatory demyelination in the brain, where very-long-chain fatty acids accumulate within phospholipid fractions such as lysophosphatidylcholine...
  2. pmc Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation
    Se Hoon Choi
    Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA
    Neuron 59:568-80. 2008
    ....
  3. pmc BAFF/APRIL system in pediatric OMS: relation to severity, neuroinflammation, and immunotherapy
    Michael R Pranzatelli
    Department of Neurology, National Pediatric Myoclonus Center and Neuroimmunology Laboratory, and Southern Illinois University School of Medicine, PO Box 19643, Springfield, IL 62794 9643, USA
    J Neuroinflammation 10:10. 2013
    ..B-cell dysregulation has been implicated but not fully characterized in pediatric opsoclonus-myoclonus syndrome (OMS), a neuroblastoma-associated neuroinflammatory disorder...
  4. pmc IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils
    Carine Savarin
    Department of Neurosciences NC30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Neuroinflammation 9:104. 2012
    ..These interactions have hindered the ability to distinguish the relative contributions of neutrophils, Th1 and Th17 cell-derived effector molecules from secondary mediators to tissue damage and morbidity...
  5. ncbi The anatomical and cellular basis of immune surveillance in the central nervous system
    Richard M Ransohoff
    Neuroinflammation Research Center and Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Nat Rev Immunol 12:623-35. 2012
    ..Furthermore, we propose a new model to explain how antigen-specific T cell responses occur in the CNS...
  6. doi Animal models of multiple sclerosis: the good, the bad and the bottom line
    Richard M Ransohoff
    Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
    Nat Neurosci 15:1074-7. 2012
    ....
  7. pmc Innate immunity in the central nervous system
    Richard M Ransohoff
    Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Clin Invest 122:1164-71. 2012
    ....
  8. pmc Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis
    D R Huang
    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
    J Exp Med 193:713-26. 2001
    ....
  9. pmc Human cerebrospinal fluid contains CD4+ memory T cells expressing gut- or skin-specific trafficking determinants: relevance for immunotherapy
    Pia Kivisakk
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA
    BMC Immunol 7:14. 2006
    ....
  10. ncbi Natalizumab for multiple sclerosis
    Richard M Ransohoff
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute and Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, OH 44195, USA
    N Engl J Med 356:2622-9. 2007
  11. pmc Chemokines in and out of the central nervous system: much more than chemotaxis and inflammation
    Astrid E Cardona
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Leukoc Biol 84:587-94. 2008
    ..We also propose novel functions of chemokine receptors during demyelination/remyelination, and developmental processes...
  12. doi Microglial physiology: unique stimuli, specialized responses
    Richard M Ransohoff
    Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Annu Rev Immunol 27:119-45. 2009
    ..Manipulating the effector functions of microglia has the potential to modify the outcome of diverse neurological diseases...
  13. ncbi The chemokine system in neuroinflammation: an update
    R M Ransohoff
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Infect Dis 186:S152-6. 2002
    ..Animal models of CNS demyelinating disease and the corresponding human disorder, multiple sclerosis are both considered...
  14. ncbi Growth factor treatment of demyelinating disease: at last, a leap into the light
    Richard M Ransohoff
    Depts of Neurosciences and Nerology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, OH 44195, USA
    Trends Immunol 23:512-6. 2002
    ....
  15. ncbi Taking two TRAILS
    Richard M Ransohoff
    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Neuron 46:355-6. 2005
    ..This report poses the therapeutic challenge of facilitating TRAIL expression in the periphery while inhibiting TRAIL in the CNS...
  16. ncbi Three or more routes for leukocyte migration into the central nervous system
    Richard M Ransohoff
    The Mellen Center for Multiple Sclerosis Treatment and Research, Department of Neurology, 9500 Euclid Avenue, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Nat Rev Immunol 3:569-81. 2003
    ..We discuss three distinct routes for leukocytes to enter the CNS and consider how different populations of leukocytes use trafficking signals to gain entry...
  17. pmc Chemokines and chemokine receptors: standing at the crossroads of immunobiology and neurobiology
    Richard M Ransohoff
    Neuroinflammation Research Center Lerner Research Institute and Mellen Center for MS Treatment and Research Neurological Institute, Cleveland Clinic, Mail Code NC30, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Immunity 31:711-21. 2009
    ..The challenge is to integrate knowledge of the roles of key receptors (as well as their ligands) into a coherent account of events during pathologic processes, in order to guide therapeutic development...
  18. ncbi Chemokines in neurological trauma models
    Richard M Ransohoff
    The Lerner Research Institute, 9500 Euclid Avenue, Room NC30, Cleveland, OH 44195, USA
    Ann N Y Acad Sci 961:346-9. 2002
  19. ncbi The myeloid cells of the central nervous system parenchyma
    Richard M Ransohoff
    Neuroinflammation Research Center Department of Neurosciences, Lerner Research Institute and Mellen Center for MS Treatment and Research Neurological Institute, Cleveland Clinic, Mail Code NC30, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nature 468:253-62. 2010
    ..Excessive or chronic inflammatory responses can, however, be harmful. How microglia balance these demands, and how their behaviour can be modified to ameliorate disorders of the central nervous system, is becoming clear...
  20. pmc Chemokine expression in the central nervous system of mice with a viral disease resembling multiple sclerosis: roles of CD4+ and CD8+ T cells and viral persistence
    R M Ransohoff
    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Virol 76:2217-24. 2002
    ..Our observations indicated that chemokine expression in the CNS in this chronic viral disorder was intrinsic to the CNS innate immune response to infection and was not governed by elements of the adaptive immune system...
  21. pmc A mighty mouse: building a better model of multiple sclerosis
    Richard M Ransohoff
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Clin Invest 116:2313-6. 2006
    ..The studies describe an important new model for MS research...
  22. pmc Regulation of tau pathology by the microglial fractalkine receptor
    Kiran Bhaskar
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Neuron 68:19-31. 2010
    ..Taken together, our results suggest that CX3CR1 and IL-1/p38 MAPK may serve as novel therapeutic targets for human tauopathies...
  23. ncbi Cortical demyelination in PML and MS: Similarities and differences
    N M Moll
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute and Neurological Institute, Cleveland Clinic NC 30, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Neurology 70:336-43. 2008
    ..To characterize pathologic changes in the cerebral cortex of patients with multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML)...
  24. ncbi The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration
    Hui Hsin Tsai
    Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    Cell 110:373-83. 2002
    ..These data suggest that population of presumptive white matter by oligodendrocyte precursors is dependent on localized expression of CXCL1...
  25. pmc CXCR2-positive neutrophils are essential for cuprizone-induced demyelination: relevance to multiple sclerosis
    Liping Liu
    Neuroinflammation Research Center, Department of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
    Nat Neurosci 13:319-26. 2010
    ..These data suggest that cuprizone-induced demyelination is useful for modeling certain aspects of multiple sclerosis pathogenesis...
  26. ncbi Chronic expression of monocyte chemoattractant protein-1 in the central nervous system causes delayed encephalopathy and impaired microglial function in mice
    DeRen Huang
    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    FASEB J 19:761-72. 2005
    ..These results indicate that huGFAP-CCL2hi tg+ mice provide a useful model to study how chronic CNS expression of CCL2 alters microglial function and CNS physiology...
  27. ncbi Pertussis toxin-induced reversible encephalopathy dependent on monocyte chemoattractant protein-1 overexpression in mice
    DeRen Huang
    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Neurosci 22:10633-42. 2002
    ..These studies characterize a novel model of reversible inflammatory encephalopathy that is dependent on both genetic and environmental factors...
  28. ncbi Control of microglial neurotoxicity by the fractalkine receptor
    Astrid E Cardona
    Neuroinflammation Research Center and Department of Neurosciences, Lerner Research Institute, Cleveland, Ohio 44195, USA
    Nat Neurosci 9:917-24. 2006
    ..Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability...
  29. ncbi Chemokines and chemokine receptors: multipurpose players in neuroinflammation
    Richard M Ransohoff
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Int Rev Neurobiol 82:187-204. 2007
    ..In some cases, the dual functions of the chemokine system in the periphery and in the CNS offer unique possibilities for disease treatment...
  30. ncbi Modulating CCR2 and CCL2 at the blood-brain barrier: relevance for multiple sclerosis pathogenesis
    Don Mahad
    Department of Neurosciences, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Brain 129:212-23. 2006
    ....
  31. ncbi Expression of chemokine receptors CCR1 and CCR5 reflects differential activation of mononuclear phagocytes in pattern II and pattern III multiple sclerosis lesions
    Don J Mahad
    Department of Neurosciences, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Neuropathol Exp Neurol 63:262-73. 2004
    ..As judged by mononuclear phagocyte chemokine receptor expression, there appear to be distinct tissue environments in pattern II and III MS lesions...
  32. ncbi VCAM-1-positive microglia target oligodendrocytes at the border of multiple sclerosis lesions
    John W Peterson
    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA
    J Neuropathol Exp Neurol 61:539-46. 2002
    ..Endothelial cells were VCAM-1-negative in both lesion and non-lesion MS brain tissue. This report is the first to document direct microglial interaction with oligodendrocytes in MS...
  33. ncbi Evidence for synaptic stripping by cortical microglia
    Bruce D Trapp
    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA
    Glia 55:360-8. 2007
    ..Since neuronal pathology was not a feature of either the acute or immune-mediated lesion, synaptic stripping by activated microglia may have neuroprotective consequences...
  34. ncbi Chemokines, mononuclear cells and the nervous system: heaven (or hell) is in the details
    Natalia M Rebenko-Moll
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Curr Opin Immunol 18:683-9. 2006
    ..Overlapping molecular signals are responsible for the migration of specific cells into the CNS during pathological inflammation and host defense, raising challenges and opportunities for therapeutic manipulation...
  35. ncbi Alterations in the oligodendrocyte lineage, myelin, and white matter in adult mice lacking the chemokine receptor CXCR2
    Dolly A Padovani-Claudio
    Department of Neurosciences, Case School of Medicine, Cleveland, Ohio 44106 6002, USA
    Glia 54:471-83. 2006
    ..Together, these findings indicate that the chemokine receptor CXCR2 is important for the development and maintenance of the oligodendrocyte lineage, myelination, and white matter in the vertebrate CNS...
  36. pmc Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin
    Pia Kivisakk
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195 Millennium Pharmaceuticals, Inc, Cambridge, MA 02142
    Proc Natl Acad Sci U S A 100:8389-94. 2003
    ....
  37. ncbi Inflammatory cell migration into the central nervous system: a few new twists on an old tale
    Shumei Man
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Brain Pathol 17:243-50. 2007
    ..The adhesion molecules and chemokine receptors provide attractive targets for neuroinflammatory diseases because of their important role in mediating central nervous system inflammation...
  38. pmc CC chemokine receptor 8 in the central nervous system is associated with phagocytic macrophages
    Corinna Trebst
    Department of Neurosciences, The Lerner Research Institute, Cleveland, Ohio 44195, USA
    Am J Pathol 162:427-38. 2003
    ..CCR8 expression may also indicate a selective program of mononuclear phagocyte gene expression...
  39. ncbi Progressive multifocal leukoencephalopathy in rheumatic diseases: evolving clinical and pathologic patterns of disease
    Leonard H Calabrese
    Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Arthritis Rheum 56:2116-28. 2007
  40. ncbi Inflammatory progressive multifocal leukoencephalopathy in human immunodeficiency virus-negative patients
    DeRen Huang
    Department of Neurology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Ann Neurol 62:34-9. 2007
    ..MRI diagnostic criteria for PML suggest that iPML does not occur in HIV-negative individuals...
  41. pmc Haploinsufficiency of utrophin gene worsens skeletal muscle inflammation and fibrosis in mdx mice
    Lan Zhou
    Department of Neurology, Cleveland Clinic, Cleveland, OH 44195, USA
    J Neurol Sci 264:106-11. 2008
    ....
  42. ncbi Interferons at age 50: past, current and future impact on biomedicine
    Ernest C Borden
    Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Rev Drug Discov 6:975-90. 2007
    ..Our goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential...
  43. pmc Localizing central nervous system immune surveillance: meningeal antigen-presenting cells activate T cells during experimental autoimmune encephalomyelitis
    Pia Kivisakk
    Center for Neurological Diseases, Brigham and Women s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Ann Neurol 65:457-69. 2009
    ..We hypothesized that activated CD4(+) T cells gain direct access to the subarachnoid space and become reactivated on encounter with cognate antigen in this compartment...
  44. pmc Imaging correlates of leukocyte accumulation and CXCR4/CXCL12 in multiple sclerosis
    Natalia M Moll
    Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Arch Neurol 66:44-53. 2009
    ..We studied the following ROIs: normal-appearing white matter (NAWM); regions abnormal only on T2-weighted images (T2 only); and regions abnormal on T2- and T1-weighted images with an abnormal magnetization transfer ratio (T2/T1/MTR)...
  45. pmc Imatinib attenuates skeletal muscle dystrophy in mdx mice
    Ping Huang
    Department of Neurology Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195 USA
    FASEB J 23:2539-48. 2009
    ..Imatinib therapy for DMD may hold promise for ameliorating muscle necrosis, inflammation, and fibrosis by inhibiting c-abl and PDGFR signaling pathways and downstream inflammatory cytokine and fibrotic gene expression...
  46. ncbi Treatment of experimental autoimmune encephalomyelitis with the chemokine receptor antagonist Met-RANTES
    Masaru Matsui
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Neuroimmunol 128:16-22. 2002
    ..Further analysis of the effects of chemokine receptor blockade may need to focus on leukocyte activation within the affected CNS as well as trafficking events...
  47. pmc Depletion of Ly6G/C(+) cells ameliorates delayed cerebral vasospasm in subarachnoid hemorrhage
    J Javier Provencio
    Neuroinflammation Research Center, Lerner Research Institute, NB3, Cleveland Clinic, 9500 Euclid Ave Cleveland, OH 44195, United States
    J Neuroimmunol 232:94-100. 2011
    ..Growing evidence supports a role for inflammation in the pathogenesis of DCV. We showed that CSF neutrophils predict which patients will develop DCV...
  48. ncbi A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica
    Claudia F Lucchinetti
    Department of Neurology, Mayo Clinic, Rochester, MN, USA
    Brain 125:1450-61. 2002
    ..Based on this study, future therapeutic strategies designed to limit the deleterious effects of complement activation, eosinophil degranulation and neutrophil/macrophage/microglial activation are worthy of further investigation...
  49. ncbi Axon loss in the spinal cord determines permanent neurological disability in an animal model of multiple sclerosis
    Jerome R Wujek
    Department of Neurosciences NC30, Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA
    J Neuropathol Exp Neurol 61:23-32. 2002
    ..This chronic-relapsing EAE model provides an excellent platform for 2 critical objectives: investigating mechanisms of axon loss and evaluating efficacy of neuroprotective therapies...
  50. ncbi Chemokine receptor CXCR3: an unexpected enigma
    Liping Liu
    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Curr Top Dev Biol 68:149-81. 2005
    ..Thus, further study is needed to determine how CXCL10 neutralizing agents or CXCR3 receptor antagonists might be applied to treating human disease...
  51. ncbi New directions in MS therapeutics: vehicles of hope
    Robert J Fox
    The Mellen Center for Multiple Sclerosis Treatment and Research, Department of Neurology, Lerner School of Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, U 10, Cleveland, OH 44195, USA
    Trends Immunol 25:632-6. 2004
    ..Dozens of therapies are in various stages of clinical development and results from these clinical studies will provide important tests of immune and inflammatory mechanisms of MS disease...
  52. pmc Myelin repair is accelerated by inactivating CXCR2 on nonhematopoietic cells
    Liping Liu
    Neuroinflammation Research Centre, Department of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Neurosci 30:9074-83. 2010
    ....
  53. ncbi CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis
    Orhun H Kantarci
    Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
    J Neuroimmunol 169:137-43. 2005
    ..Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS...
  54. ncbi The expression and function of chemokines involved in CNS inflammation
    Eroboghene E Ubogu
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Trends Pharmacol Sci 27:48-55. 2006
    ..We also discuss currently proposed and potentially useful chemokine receptor antagonists...
  55. ncbi Lysophosphatidylcholine regulates human microvascular endothelial cell expression of chemokines
    Gurunathan Murugesan
    Department of Clinical Pathology L30, The Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Mol Cell Cardiol 35:1375-84. 2003
    ....
  56. ncbi Severe disease, unaltered leukocyte migration, and reduced IFN-gamma production in CXCR3-/- mice with experimental autoimmune encephalomyelitis
    Liping Liu
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA
    J Immunol 176:4399-409. 2006
    ..CXCR3 does not govern leukocyte trafficking in EAE but modulates T cell IFN-gamma production and downstream events that affect disease severity...
  57. pmc Monocytes regulate T cell migration through the glia limitans during acute viral encephalitis
    Carine Savarin
    Department of Neuroscience NC30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland OH 44195, USA
    J Virol 84:4878-88. 2010
    ..However, monocytes facilitate penetration through the glia limitans. Thus, the rapid monocyte response to viral encephalitis constitutes an indirect antiviral pathway by aiding access of effector T cells to the site of viral infection...
  58. ncbi Analysis of leukocyte extravasation across the blood-brain barrier: conceptual and technical aspects
    Melissa K Callahan
    Department of Neurosciences, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Curr Allergy Asthma Rep 4:65-73. 2004
    ..The process of extravasation can usefully be regarded as comprising individual steps. This review is focused on the need to consider these stages separately, and the elucidation of mechanisms at each stage is outlined...
  59. ncbi CXCR3 marks CD4+ memory T lymphocytes that are competent to migrate across a human brain microvascular endothelial cell layer
    Melissa K Callahan
    Department of Neurosciences, Cleveland Clinic Foundation, NC 30 Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Neuroimmunol 153:150-7. 2004
    ..We propose that CXCR3 serves as a surface marker for cells that have the capacity to cross the BBB, but does not play an essential role in extravasation...
  60. pmc Human brain microvascular endothelial cells and umbilical vein endothelial cells differentially facilitate leukocyte recruitment and utilize chemokines for T cell migration
    Shumei Man
    Department of Neurosciences, Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Clin Dev Immunol 2008:384982. 2008
    ..These data establish baseline conditions for using THBMECs to develop in vitro BBB models for studying leukocyte-endothelial interactions during neuroinflammation...
  61. pmc alpha4 Integrin/FN-CS1 mediated leukocyte adhesion to brain microvascular endothelial cells under flow conditions
    Shumei Man
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, OH 44195, USA
    J Neuroimmunol 210:92-9. 2009
    ..These results established a novel in vitro dynamic BBB model. We also demonstrated the dependence of leukocyte-endothelial interactions in this model on alpha4 integrins and FN-CS1...
  62. ncbi The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system
    DeRen Huang
    Neuroinflammation Research Center, Department of Neurosciences NC30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, Ohio 44195, USA
    FASEB J 20:896-905. 2006
    ..These results are the first to define a chemokine that governs NK cell migration to the CNS, and the findings suggest novel therapeutic manipulation of CX3CR1+ NK cells...
  63. ncbi Flow cytometric analysis of chemokine receptor expression on cerebrospinal fluid leukocytes
    Pia Kivisakk
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Methods 29:319-25. 2003
    ..Here, we describe the methodology used in our laboratory to study chemokine receptor expression on cells in paired samples from peripheral blood and CSF using flow cytometry...
  64. ncbi Mononuclear phagocytes migrate into the murine cochlea after acoustic trauma
    Keiko Hirose
    Head and Neck Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Comp Neurol 489:180-94. 2005
    ..Immunohistochemistry demonstrates that these cochlear cells are derived from the monocyte/macrophage lineage and serve a phagocytic function in the inner ear...
  65. pmc CC chemokine receptor 2 is protective against noise-induced hair cell death: studies in CX3CR1(+/GFP) mice
    Nathan B Sautter
    Head and Neck Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    J Assoc Res Otolaryngol 7:361-72. 2006
    ..Possible mechanisms of neuroprotection by CCR2 are discussed...
  66. ncbi Expression of CCR7 in multiple sclerosis: implications for CNS immunity
    Pia Kivisakk
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Ann Neurol 55:627-38. 2004
    ..These data suggested that the efferent limb of CNS immunity is executed by central-memory T cells, which enter CSF directly from the circulation...
  67. pmc CCR5 expression on monocytes and T cells: modulation by transmigration across the blood-brain barrier in vitro
    Eroboghene E Ubogu
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Cell Immunol 243:19-29. 2006
    ....
  68. ncbi Requirement of phosphoinositide 3-kinase and Akt for interferon-beta-mediated induction of the beta-R1 (SCYB11) gene
    M R Sandhya Rani
    Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 277:38456-61. 2002
    ..The results provide novel insight into the role of PI3K in the transcriptional response to IFN-beta...
  69. ncbi Repopulation of cochlear macrophages in murine hematopoietic progenitor cell chimeras: the role of CX3CR1
    Eisuke Sato
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Comp Neurol 506:930-42. 2008
    ..Furthermore, CX3CR1 in hematopoietic precursors is not necessary for macrophage migration into cochlea and when deleted in this cell population, the absence of CX3CR1 does not substantially effect the outcomes after noise...
  70. ncbi Cutting edge: the silent chemokine receptor D6 is required for generating T cell responses that mediate experimental autoimmune encephalomyelitis
    Liping Liu
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Immunol 177:17-21. 2006
    ..CD11c(+) dendritic cells accumulated abnormally in cutaneous immunization sites of D6(-/-) mice. Surprisingly, D6, a "silent" chemokine receptor, supports immune response generation...
  71. ncbi The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE)
    Don J Mahad
    Department of Neurosciences, Mail Code NC30, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Semin Immunol 15:23-32. 2003
    ..Hence, CCL2 and CCR2 may be targets for specific and effective treatment in MS...
  72. ncbi Interferon-beta 1a does not reduce expression of CCR5 and CXCR3 on circulating T cells
    Pia Kivisakk
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Neuroimmunol 141:150-4. 2003
    ....
  73. pmc Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis
    Zizhen Kang
    Department of Immunology, Cleveland Clinic, Cleveland, OH 44195, USA
    Immunity 32:414-25. 2010
    ..Specifically, Act1-deficient astrocytes showed impaired IL-17-mediated inflammatory gene induction. Thus, astroctyes are critical in IL-17-Act1-mediated leukocyte recruitment during autoimmune-induced inflammation of the CNS...
  74. ncbi Defining interferon beta response status in multiple sclerosis patients
    Richard A Rudick
    Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, OH 44195, USA
    Ann Neurol 56:548-55. 2004
    ..MRI classification may facilitate rational therapeutic decisions, better clinical trial designs, and studies correlating biomarkers with therapeutic response...
  75. ncbi The CD4-Th1 model for multiple sclerosis: a critical [correction of crucial] re-appraisal
    Hans Lassmann
    Division of Neuroimmunology, Brain Research Institute, University of Vienna, Spitalgasse 4, A 1090 Vienna, Austria
    Trends Immunol 25:132-7. 2004
  76. ncbi Multiple sclerosis: a study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system
    Torben L Sørensen
    The MS Clinic, Department of Neurology, University of Copenhagen, Glostrup Hospital, 2600 Glostrup, Denmark
    J Neuroimmunol 127:59-68. 2002
    ..These data suggest a critical role for CXCL10 and CXCR3 in the accumulation of T cells in the CNS of MS patients...
  77. ncbi The many roles of chemokines and chemokine receptors in inflammation
    Israel F Charo
    Gladstone Institute of Cardiovascular Disease and the Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, San Francisco, USA
    N Engl J Med 354:610-21. 2006
  78. ncbi Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10
    Bernd C Kieseier
    Department of Neurology, Karl Franzens University, Graz, Austria
    Brain 125:823-34. 2002
    ..Our results imply a pathogenic role for specific chemokine receptors and IP-10 in the genesis of inflammatory demyelinating neuropathies...
  79. ncbi Monocyte recruitment and myelin removal are delayed following spinal cord injury in mice with CCR2 chemokine receptor deletion
    Manhong Ma
    Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio, USA
    J Neurosci Res 68:691-702. 2002
    ..Together, these results indicate that chemokines acting through CCR2 contribute to the early recruitment of monocytes to the lesion epicenter following SCI...
  80. ncbi Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment
    Markus Krumbholz
    Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany
    Brain 129:200-11. 2006
    ..Therefore, both CXCL13 and CXCR5 may be promising therapeutic targets in multiple sclerosis...
  81. ncbi Experimental autoimmune encephalomyelitis: CC chemokine receptor expression by trafficking cells
    Andrzej R Glabinski
    Department of Neurology, Medical University of Lodz, ul Kopcinskiego 22, 90 153, Łódź, Poland
    J Autoimmun 19:175-81. 2002
    ..The principal cells expressing CCR5 were inflammatory cells invading the spinal cord. Our results supported the implication of Th1-associated CCRs in the CNS-specific inflammatory reaction of ChREAE...
  82. ncbi Comparison of ventricular and lumbar cerebrospinal fluid T cells in non-inflammatory neurological disorder (NIND) patients
    J Javier Provencio
    Department of Neurosciences, NC30, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Neuroimmunol 163:179-84. 2005
    ..These observations support the hypothesis that leukocytes enter the CSF in a selective fashion, at its site of formation in the choroid plexus. The results implicate CSF T cells in the immune surveillance of the central nervous system...
  83. ncbi Inflammatory disease: assault on the guardian
    Richard M Ransohoff
    Nature 448:421-2. 2007
  84. ncbi Recovery from EAE is associated with decreased survival of encephalitogenic T cells in the CNS of B7-1/B7-2-deficient mice
    Tammy T Chang
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA
    Eur J Immunol 33:2022-2032. 2003
    ....
  85. ncbi Interleukin-6 protects anterior horn neurons from lethal virus-induced injury
    Kevin D Pavelko
    Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Neurosci 23:481-92. 2003
    ..These data support the hypothesis that IL-6 plays a critical role in protecting specific populations of neurons from irreversible injury...
  86. pmc Overexpression of monocyte chemotactic protein-1/CCL2 in beta-amyloid precursor protein transgenic mice show accelerated diffuse beta-amyloid deposition
    Masaru Yamamoto
    Center for Neurovirology and Neurodegenerative Disorders and Department of Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska 68198 5880, USA
    Am J Pathol 166:1475-85. 2005
    ..Understanding the mechanisms underlying these events could be used to modulate microglial function in Alzheimer's disease and positively affect disease outcomes...
  87. ncbi Leukemia inhibitory factor deficiency modulates the immune response and limits autoimmune demyelination: a new role for neurotrophic cytokines in neuroinflammation
    Ralf A Linker
    Institute for Multiple Sclerosis Research, University of Goettingen and Gemeinnuetzige Hertie Stiftung, Goettingen, Germany
    J Immunol 180:2204-13. 2008
    ..These data reveal that endogenous LIF is an immunologically active molecule in neuroinflammation. This establishes a link between LIF and the immune system which was not observed in the ciliary neurotrophic factor knockout mouse...
  88. ncbi The Epstein-Barr virus oncoprotein latent membrane protein 1 induces expression of the chemokine IP-10: importance of mRNA half-life regulation
    Martina Vockerodt
    Zentrum Kinderheilkunde und Jugendmedizin, Abteilung Pädiatrie I, Georg August Universitat, Gottingen, Germany
    Int J Cancer 114:598-605. 2005
    ..This new mechanism of gene regulation demonstrates the potential of the oncoprotein LMP1 to orchestrate a network of signalling pathways at different regulatory levels including mRNA stability...
  89. ncbi A novel model of demyelinating encephalomyelitis induced by monocytes and dendritic cells
    Glaucia C Furtado
    Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029 6574, USA
    J Immunol 177:6871-9. 2006
    ..We propose that alterations in the numbers or function of monocytes and DC coupled to dysregulated expression of chemokines in the neural tissues, favors development of CNS autoimmune disease...
  90. doi CCL2 recruitment of IL-6-producing CD11b+ monocytes to the draining lymph nodes during the initiation of Th17-dependent B cell-mediated autoimmunity
    Ying Bai
    Institute of Neuroinformatics and Laboratory for Brain and Mind, Dalian University of Technology, Dalian, China
    Eur J Immunol 38:1877-88. 2008
    ..Thus, Th17 cells can promote humoral autoimmunity via a novel mechanism that involves CCL2...
  91. ncbi TNF-alpha microinjection upregulates chemokines and chemokine receptors in the central nervous system without inducing leukocyte infiltration
    Andrzej R Glabinski
    Department of Neurology, Medical University of Lodz, Lodz, Poland
    J Interferon Cytokine Res 23:457-66. 2003
    ..This observation shows that upregulation of chemokines by TNF-alpha is not sufficient to cause accumulation of leukocytes in the CNS parenchyma in both strains of mice...
  92. ncbi CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler's murine encephalomyelitis virus-induced demyelinating disease
    Jami L Bennett
    Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurovirol 9:623-36. 2003
    ..These results suggest that CCL2 expression in the CNS is a major pathogenic factor that drives macrophage accumulation in the development of CNS inflammatory disease...

Research Grants22

  1. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2001
    ..4. Regulation of MCP-1 transcription by constitutive and inducible factors. Data gained from these experiments will provide a rational foundation for strategies to modulate chemokine expression during neurological disease states. ..
  2. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2005
    ..How do CXCR3 and its ligands govern the accumulation and distribution of T-cells in the CNS of mice with EAE? ..
  3. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2002
    ..How do CXCR3 and its ligands govern the accumulation and distribution of T-cells in the CNS of mice with EAE? ..
  4. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2004
    ..How do CXCR3 and its ligands govern the accumulation and distribution of T-cells in the CNS of mice with EAE? ..
  5. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2009
    ..Ongoing clinical trials for pulmonary disease use drugs that block CXCR2 and our studies will provide essential data for designing clinical trials of CXCR2 blockade in MS. ..
  6. Gender differences in immune responses in MS
    Richard Ransohoff; Fiscal Year: 2009
    ....
  7. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2006
    ..How do CXCR3 and its ligands govern the accumulation and distribution of T-cells in the CNS of mice with EAE? ..
  8. Chemokine Regulation on Central Nervous System Inflammation in Multiple Sclerosis
    Richard Ransohoff; Fiscal Year: 2007
    ..Formal classwork and informal guidance are integrated in the mentoring plan, which will result in development of clinician-scientists who are enabled to use cutting edge research techniques to elucidate human disease. ..
  9. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2005
    ..How do CXCR3 and its ligands govern the accumulation and distribution of T-cells in the CNS of mice with EAE? ..
  10. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2003
    ..How do CXCR3 and its ligands govern the accumulation and distribution of T-cells in the CNS of mice with EAE? ..
  11. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 2000
    ..4. Regulation of MCP-1 transcription by constitutive and inducible factors. Data gained from these experiments will provide a rational foundation for strategies to modulate chemokine expression during neurological disease states. ..
  12. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 1999
    ..4. Regulation of MCP-1 transcription by constitutive and inducible factors. Data gained from these experiments will provide a rational foundation for strategies to modulate chemokine expression during neurological disease states. ..
  13. CHEMOKINES IN CNS INFLAMMATION
    Richard Ransohoff; Fiscal Year: 1999
    ..4. Regulation of MCP-1 transcription by constitutive and inducible factors. Data gained from these experiments will provide a rational foundation for strategies to modulate chemokine expression during neurological disease states. ..
  14. CHEMOKINES IN CNS INFLAMMATION
    Richard M Ransohoff; Fiscal Year: 2010
    ..Ongoing clinical trials for pulmonary disease use drugs that block CXCR2 and our studies will provide essential data for designing clinical trials of CXCR2 blockade in MS. ..