Myelin damage and repair in pathologic CNS: challenges and prospects.

摘要: Injury to the central nervous system (CNS) results in oligodendrocyte cell death and progressive demyelination. Demyelinated axons undergo considerable physiological changes molecular reorganizations that collectively result axonal dysfunction, degeneration loss of sensory motor functions. Endogenous adult precursor cells neural stem/progenitor contribute replacement oligodendrocytes, however, extent quality endogenous remyelination is suboptimal. Emerging evidence indicates optimal restricted by multiple factors including (i) low levels promote oligodendrogenesis; (ii) among newly generated (iii) inhibitory post-injury milieu impede remyelination, (iv) deficient expression key growth essential for proper re-construction a highly organized myelin sheath. Considering these challenges, over past several years, number cell-based strategies have been developed optimize therapeutically. Outcomes basic preclinical discoveries are promising signify importance as mechanism improving functions CNS injuries. In this review, we provide an overview on: (1) precise organization myelinated reciprocal axo-myelin interactions warrant properly balanced activities within CNS; (2) underlying cause demyelination structural functional consequences following injury disease; (3) mechanisms replacement; (4) modulatory role reactive astrocytes inflammatory remyelination; (5) current status therapies promoting remyelination. Careful elucidation cellular pathologic better understanding impact repair.