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Dr. Bruce Trapp - With age and aging of a lesion, OPC levels and remyelination capacity decrease
Dr. Bruce Trapp, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA, shares the latest insights in the differences of remyelination capacity in MS lesions present at different locations in the brain.
Demyelination also destroys oligodendrocytes, therefore new oligodendrocytes have to be produced to enable remyelination. The brain is able to produce new oligodendrocytes and remyelinate MS lesions, but in most lesions this is not occurring. This is most likely not due to a lack in oligodendrocyte progenitor cells (OPCs), as these are still present in all lesions, although numbers may be reduced. Also, the OPC can generate myelin protein expressing cells that still do not remyelinate. With age of a patient but also with aging of a lesion, OPC levels and the remyelination capacity decrease. This hold especially true for white matter lesions, as in cortical or grey matter lesions no decreased capacity is detected with aging. Comparing these two environments with differences in remodeling capacities may allow for the identification of inhibiting and/or stimulating factors of remyelination. Instrumental in such studies are so-called Type I that contain both white and grey matter, as the lesion age is now identical in both areas. In such lesions it is seen that the grey matter is remyelinating, while white matter is not. Probably both inhibitors (in white matter) and promotors (in grey matter) of remyelination are at play. Currently, most is known about inhibitors. For instance, the extracellular matrix proteins sulfate proteoglycans found in higher levels in white matter, has been found to inhibit oligodendrocyte differentiation and myelination in vitro as well as in animal studies. Such molecules are promising targets for drug development, e.g. using specific enzymes that break down this molecule. What factors differ? Grey matter may express stimulating or white is expressing inhibiting. Probably both, more known about inhibitors (extracellular matrix proteins). sulfate proteoglycans in white matter lesions – can hibit in vitro and in animal models oligo differentiation and mylenation, Major suspect. Promissing targets for e.g. enzymes breaking down this molecule. Grey matter does not express this much. Future efforts will be directed at unraveling why the cortex has such a remodeling ability. Such insights may help us push this activity in white matter, or allow us to stimulate grey matter to remodel more. The new insights show that the brain never gives up to repair the brain – neither should the patients!