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Potential mechanisms of failure to remyelinate the damaged white matter. Inflammation, oxidative stress and hypoxia induced demyelination. OPC proliferate to attempt remyelination. High molecular weight hyaluronic acid (HMW-HA) produced by reactive astrocytes is cleaved by the hyaluronidase PH20 generating digestion products that inhibit OPC maturation through mechanisms involving TLR2 and 4 and GSK3β. The resulting OPC maturation arrest prevents efficient remyelination.
