title: The challenges of long-distance axon regeneration in the injured CNS.
abstract: Injury to the central nervous system (CNS) that results in long-tract axonal damage typically leads to permanent functional deficits in areas innervated at, and below, the level of the lesion. The initial ischemia, inflammation, and neurodegeneration are followed by a progressive generation of scar tissue, dieback of transected axons, and demyelination, creating an area inhibitory to regrowth and recovery. Two ways to combat this inhibition is to therapeutically target the extrinsic and intrinsic properties of the axon-scar environment. Scar tissue within and surrounding the lesion site can be broken down using an enzyme known as chondroitinase. Negative regulators of adult neuronal growth, such as Nogo, can be neutralized with antibodies. Both therapies greatly improve functional recovery in animal models. Alternatively, modifying the intrinsic growth properties of CNS neurons through gene therapy or pharmacotherapy has also shown promising axonal regeneration after injury. Despite these promising therapies, the main challenge of long-distance axon regeneration still remains; achieving a level of functional and organized connectivity below the level of the lesion that mimics the intact CNS.
authors.affiliation: Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Chew
authors.forename: James W
authors.initials: JW
authors.lastname: Fawcett
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Andrews
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D017690:Cell Transplantation / Q000379:methods*; D002493:Central Nervous System Diseases / Q000473:pathology / Q000601:surgery*; D006801:Humans; D009416:Nerve Regeneration / Q000502:physiology*