Injury-related dynamic myelin/oligodendrocyte axon-outgrowth inhibition in the central nervous system.
BACKGROUND
By contrast with the glial scar, myelin was considered a constitutive static inhibitory barrier unreactive to lesions in the central nervous system (CNS). However, recent results suggest considerable add-on inhibition of myelin as a result of CNS injury. Furthermore, catastrophic events cause morphological and biochemical changes in the axon itself. This results in the accumulation of cytoskeleton components and intraaxonal transported proteins paralleled by extensive membrane remodelling at the axonal tip (a process called axotomy) which might modify the axonal response to its inhibitory environment.


BACKGROUND
Ji-Eun Kim and colleagues recently reported an axonal subpopulation with a different capacity to respond to myelin inhibitors (Neuron 2004; 44: 439-51). Axonal specificity but also evidence for injury reactivity summarised here challenges our understanding of axon-growth inhibition in the injured CNS. This might be due to (i) qualitative and quantitative enrichment of the periaxonal environment by myelin/oligodendrocytes, (ii) increased axonal sensitivity to its inhibitory environment, and (iii) axons and lesion-induced, altered axonal signalling. WHERE NEXT? Postlesional reactive inhibition of myelin or the oligodendrocyte necessitates the development of novel screening approaches and therapeutic agents to promote axonal regeneration. Moreover, we need to improve our understanding of the pathophysiology of the lesion to find more efficient experimental strategies to restore neurological function.
Schwab
Jan M
JM
Equipe Développement Neuronal, CNRS UMR 7102, Université Pierre et Marie Curie (Paris 6), Paris, France. Jschwab@zeus.bwh.harvard.edu
Failli
Vieri
V
Chédotal
Alain
A
D000818:Animals; D001369:Axons / Q000502:physiology*; D002490:Central Nervous System / Q000293:injuries*; D006801:Humans; D007249:Inflammation; D009185:Myelin Proteins / Q000502:physiology; D009186:Myelin Sheath / Q000502:physiology*; D018992:Myelin-Associated Glycoprotein / Q000502:physiology; D009416:Nerve Regeneration; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000502:physiology*
D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D000070798:Nogo Proteins; C000603199:RTN4 protein, human