<P> Neuroregeneration in the peripheral nervous system (PNS) occurs to a significant degree . After an injury to the axon, peripheral neurons activate a variety of signaling pathways which turn on pro-growth genes, leading to reformation of a functional growth cone and regeneration . The growth of these axons is also governed by chemotactic factors secreted from Schwann cells . Injury to the peripheral nervous system immediately elicits the migration of phagocytes, Schwann cells, and macrophages to the lesion site in order to clear away debris such as damaged tissue which is inhibitory to regeneration . When a nerve axon is severed, the end still attached to the cell body is labeled the proximal segment, while the other end is called the distal segment . After injury, the proximal end swells and experiences some retrograde degeneration, but once the debris is cleared, it begins to sprout axons and the presence of growth cones can be detected . The proximal axons are able to regrow as long as the cell body is intact, and they have made contact with the Schwann cells in the endoneurial channel or tube . Human axon growth rates can reach 1 mm / day in small nerves and 5 mm / day in large nerves . The distal segment, however, experiences Wallerian degeneration within hours of the injury; the axons and myelin degenerate, but the endoneurium remains . In the later stages of regeneration the remaining endoneurial tube directs axon growth back to the correct targets . During Wallerian degeneration, Schwann cells grow in ordered columns along the endoneurial tube, creating a band of Büngner (boB) that protects and preserves the endoneurial channel . Also, macrophages and Schwann cells release neurotrophic factors that enhance re-growth . </P> <P> Unlike peripheral nervous system injury, injury to the central nervous system is not followed by extensive regeneration . It is limited by the inhibitory influences of the glial and extracellular environment . The hostile, non-permissive growth environment is, in part, created by the migration of myelin - associated inhibitors, astrocytes, oligodendrocytes, oligodendrocyte precursors, and microglia . The environment within the CNS, especially following trauma, counteracts the repair of myelin and neurons . Growth factors are not expressed or re-expressed; for instance, the extracellular matrix is lacking laminins . Glial scars rapidly form, and the glia actually produce factors that inhibit remyelination and axon repair; for instance, NOGO and NI - 35 . The axons themselves also lose the potential for growth with age, due to a decrease in GAP 43 expression among others . </P> <P> Slower degeneration of the distal segment than that which occurs in the peripheral nervous system also contributes to the inhibitory environment because inhibitory myelin and axonal debris are not cleared away as quickly . All these factors contribute to the formation of what is known as a glial scar, which axons cannot grow across . The proximal segment attempts to regenerate after injury, but its growth is hindered by the environment . It is important to note that central nervous system axons have been proven to regrow in permissive environments; therefore, the primary problem to central nervous system axonal regeneration is crossing or eliminating the inhibitory lesion site . Another problem is that the morphology and functional properties of central nervous system neurons are highly complex, for this reason a neuron functionally identical cannot be replaced by one of another type (Llinás' law). </P> <P> Glial cell scar formation is induced following damage to the nervous system . In the central nervous system, this glial scar formation significantly inhibits nerve regeneration, which leads to a loss of function . Several families of molecules are released that promote and drive glial scar formation . For instance, transforming growth factors B - 1 and - 2, interleukins, and cytokines play a role in the initiation of scar formation . The accumulation of reactive astrocytes at the site of injury and the up regulation of molecules that are inhibitory for neurite outgrowth contribute to the failure of neuroregeneration . The up - regulated molecules alter the composition of the extracellular matrix in a way that has been shown to inhibit neurite outgrowth extension . This scar formation involves several cell types and families of molecules . </P>

How long does it take for neurons to regenerate