was first observed in cat models. It was later discovered to occur in the human CNS as well, specifically in cases of multiple sclerosis (MS). Spontaneous myelin repair does not result in morphologically normal oligodendrocytes and is associated with thinner myelin compared to axonal diameter than normal myelin. Despite morphological abnormalities, however, remyelination does restore normal conduction. In addition, spontaneous remyelination does not appear to be rare, at least in the case of MS. Studies of MS lesions reported the average extent of remyelination as high as 47%. Comparative studies of cortical lesions reported a greater proportion of remyelination in the cortex as opposed to white matter lesions. OPCs retain the ability to proliferate in adulthood and comprise 70-90% of the proliferating cell population in the mature CNS. Under conditions in the developing and mature CNS where a reduction in the normal number of oligodendrocytes or myelin occurs, OPCs react promptly by undergoing increased proliferation. Rodent OPCs proliferate in response to demyelination in acute or chronic lesions created by chemical agents such as lysolecithin or cuprizone, and newborn cells differentiate into remyelinating oligodendrocytes. Similarly, OPCs proliferation occurs in other types of injury that are accompanied by loss of myelin, such as spinal cord injury. Despite OPCs' potential to give rise to myelinating oligodendrocytes, complete myelin regeneration is rarely observed clinically or in chronic experimental models. Possible explanations for remyelination failure include depletion of OPCs over time, failure to recruit OPCs to the demyelinated lesion, and failure of recruited OPCs to differentiate into mature oligodendrocytes (reviewed in ). In fresh MS lesions, clusters of HNK-1+ oligodendrocytes have been observed, which suggests that under favorable conditions OPCs expand around demyelinated lesions and generate new oligodendrocytes. In chronic MS lesions where remyelination is incomplete, there is evidence that there are oligodendrocytes with processes extending toward demyelinated axons, but they do not seem to be able to generate new myelin. The mechanisms that regulate differentiation of OPCs into myelinating oligodendrocytes are an active area of research. Another unanswered question is whether the OPC pool eventually becomes depleted after it is used to generate remyelinating cells. Clonal analysis of isolated OPCs in the normal mouse forebrain suggests that in the adult, most clones originating from single OPCs consist of either a heterogeneous population containing both oligodendrocytes and OPCs or consist exclusively of OPCs, suggesting that OPCs in the adult CNS are able to self-renew and