Late Remyelination

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Remyelination in chronic lesions may be restricted to the plaque edge or may extend throughout the lesion (Figure 7). Such lesions, referred to as shadow plaques, consist of sharply demarcated areas of complete remyelination, and are characterized by reduced staining of myelin (myelin pallor) due to a decreased ratio between myelin

Figure 7 (See color insert.) Remyelination in chronic multiple sclerosis is characterized by the reduced staining intensity of myelin and may be restricted to the lesion edge (A; MBP) or present throughout the lesion (B, "shadow-plaque"; LFB/PAS). Abbreviation: LFB/ PAS, luxol fast blue/periodic acid schif. Source: From Ref. 163.

Figure 7 (See color insert.) Remyelination in chronic multiple sclerosis is characterized by the reduced staining intensity of myelin and may be restricted to the lesion edge (A; MBP) or present throughout the lesion (B, "shadow-plaque"; LFB/PAS). Abbreviation: LFB/ PAS, luxol fast blue/periodic acid schif. Source: From Ref. 163.

sheath thickness and axonal diameter. These late remyelinating lesions typically contain few macrophages, and are typically associated with profound fibrillary gliosis. These remyelinated lesions may subsequently become targets of new demyelinating attacks (50).

The presence of cells in very early stages of oligodendrocyte development identified in completely demyelinated plaques devoid of mature oligodendrocytes, as well as in chronic lesions devoid of remyelination (51), suggests that the failure of remyelination at these later disease phases is not due to a lack of oligodendrocyte progenitors, as is the case in early remyelinating MS lesions, but rather the lesion microenvironment may not be receptive to remyelination signals (52). Whether this is due to an imbalance of growth factors, an abnormal composition of axons, glial scarring, or impaired axon-oligodendrocyte interaction is uncertain. To what extent progenitor cells already present within chronic MS lesions can be stimulated to divide, repopulate the lesion, and initiate remyelination must still be determined.

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