PATHOGENESIS AND TREATMENT OF MULTIPLE SCLEROSIS

  • Shafit-Zagardo, Bridget (PI)
  • Traugott, U.T.E. (PI)
  • Bornstein, Murray (PI)
  • Brosnan, Celia (PI)
  • Raine, Cedric (PI)
  • Traugott, U.T.E. (PI)
  • Brosnan, Celia (PI)
  • Raine, Cedric (PI)
  • Shafit-Zagardo, Bridget (PI)

Project: Research project

Project Details

Description

The proposed program extends and develops further investigations into
immunopathogenesis of the demyelinative disorders and the structural and
functional effects of those factors. Project I- will examine the effects
of lymphokines, T-cells and serum on the integrity of myelin in
organotypic cultures as determined by immunocytochemical and structural
observations. Co-cultures of CNS fragments and endothelial cells will be
established in an in vitro counterpart of our previous studies of the
blood-brain barrier. Project II- will involve the expression, cellular
localization and immunopathologic effects of products of the immune
system that may act in immune-mediated demyelination by means of
ultrastructural and immunocyte chemical techniques applied to cultured
tissues affected by lymphocytes, T-cell lines and cytokines. Project
III -will involve continuations of analyses of passively transferred EAE
using new markers (T-200, PMN leucocytes, interleukin-2) and transferrin
receptors, interleukins, interferons and tumor necrosis factor, adhesion
molecules, and receptors for high endothelial venules, organotypic
cultures will be used to examine the roles of various growth factors, and
adhesion molecules during demyelination and remyelination. ProjectIV-
will examine epidural visual evoked potentials, direct intracranial
recordings of unit activity within tracts and cortex will be combined
with monocular injection of cytokines and antibodies against specific CNS
antigens. Project V- Will explore in greater detail the role of cytokines
in inducing changes in the cerebral vasculature leading to inflammation
of the CNS. Biological assays and molecular biological techniques will be
used. Project VI- will assess GFAP mRNA levels as they may parallel GFA
protein by in situ hybridization analysis in sections of Lewis rat cord
and brain and in primary rat astrocyte cultures and human astrocytoma
cell line HTB-17. Core A- will supply organtoypic cultures for this
program and, in addition, will establish cultures of endothelial cells
and CNS tissue.
StatusFinished
Effective start/end date1/1/905/31/90

Funding

  • National Institute of Neurological Disorders and Stroke

ASJC

  • Neurology
  • Earth-Surface Processes
  • Medical Laboratory Technology
  • Development
  • Materials Chemistry
  • Cellular and Molecular Neuroscience
  • Molecular Medicine
  • Developmental Neuroscience
  • Nutrition and Dietetics
  • Structural Biology
  • Biochemistry
  • Behavioral Neuroscience
  • Hardware and Architecture
  • Cell Biology
  • Pathology and Forensic Medicine
  • Immunology and Allergy
  • Rheumatology
  • Nuclear Energy and Engineering
  • Pharmacology
  • Histology
  • Immunology
  • Developmental Biology

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.