Figure 9. Phenomenological model of the origin and fate of the phase rim.

In this hypothetical model, peripheral macrophages and activated microglia are recruited to the site of tissue damage (i). The potential roles of proinflammatory macrophages and microglia are shown in ii and iii: clearance of myelin debris, removal of free iron derived from the demyelinating process, production of free radicals, induction of the glial scar, and recruitment of oligodendrocyte precursors. The healing process is mediated by the shift from proinflammatory to antiinflammatory macrophages/microglia induced by interaction with the extracellular matrix and other factors (iv). Antiinflammatory macrophages/microglia help limit formation of a glial scar and promote migration of oligodendrocyte precursor cells into the demyelinated lesion (v), where they can mature into myelinating oligodendrocytes (vi) and remyelinate naked axons (vii). Any interruption of the healing process (e.g., failure of macrophages/microglia to acquire a fully antiinflammatory phenotype and subsequently clear macrophages/microglia) might trigger a vicious circle, resulting in persistence of the phase rim over at least the first year of lesion evolution.