the role of oligodendrocytes in maintaining the distribution of sodium channels in axons;
the mechanisms that disable and destroy oligodendrocytes in MS;
how and to what extent progenitor cells are induced to become oligodendrocytes that remyelinate axons; and
the relationship between demyelination, injury to axons, and neuropathic pain in MS, and demyelination and axon injury in appropriate animal models.
Specific needs for research on astrocytes include the following:
Astrocytes as antigen-presenting cells. To what extent do astrocytes participate in the immunopathogenesis of MS? Is there an underlying disorder of astrocyte function in MS?
Astrocytes as producers of cytokines, chemokines or other molecules that influence blood-brain barrier permeability, immune cells, or myelin. Astrocyte response to neurotrophins should also be studied.
Astrocytes as scarring cells. Do scarring astrocytes inhibit remyelination or regeneration of axons in MS? If so, can this process be controlled?
Astrocytes as regulators of axonal conduction. The possible role of astrocytes as producers of sodium channels that are transferred to demyelinated axons should be explored.
Astrocytes as homeostatic regulators of the neuronal microenvironment. It is now well known that astrocytes can regulate the levels of biologically important ions, neurotransmitters, and related molecules in the healthy nervous system. Better understanding of this role of astrocytes in MS is needed.
Specific needs for research on interaction between neural and immune cells include:
more complete delineation of the mechanisms by which the immune system contributes to demyelination and remyelination;
interaction of T cells and antibodies with axons and neuron cell bodies;
identification of the humoral factors that increase the permeability of the blood-brain barrier, thereby allowing the trafficking of immune cells through the brain; and
evidence that immune cells destroy oligodendrocytes through the excita-