Animal studies are now showing the exciting potential to achieve significant functional recovery following central nervous system (CNS) injury by manipulating both the inefficient intracellular growth machinery in neurons, as well as the extracellular barriers, which further limit their regenerative potential. In this review, we have focused on the three major glial cell types: oligodendrocytes, astrocytes, and microglia/macrophages, in addition to some of their precursors, which form major extrinsic barriers to regrowth in the injured CNS. Although axotomized neurons in the CNS have, at best, a limited capacity to regenerate or sprout, there is accumulating evidence that even in the adult and, especially after boosting their growth motor, neurons possess the capacity for considerable circuit reorganization and even lengthy regeneration when these glial obstacles to neuronal regrowth are modified, eliminated, or overcome.
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