神経薬理・シリーズ教育講座　　４．ほ乳動物中枢神経伝導路の再生

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  • Regeneration of the Mammalian CNS Pathway.

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Contrary to the current concept of abortive regeneration of mammalian central axons, marked and functionally active regeneration of the mammalian CNS pathway has been found to occur. In addition, the concept seems to be now widely accepted that the axonal environment is non-permissive for regeneration because of inhibitory activity derived from oligodendrocytes and CNS myelin, and that therefore, those procedures that render the environment permissive for regeneration are essential, e.g., graft of peripheral nerves, Schwann cells or olfactory ensheathing cells, and application of antibody for neurite growth inhibitors with or without neurotrophic factor. However, this idea is not true. These procedures led to sparse, dispersed and largely aberrant regeneration. By contrast, in our experiment using a young rat, a very sharp cut of the pyramidal tract at the level of the medulla produced edema-free lesions without subse-quent formation of either cysts or scars, and eventuated marked regeneration, very close to normal in the amount, extension, path, formation of a compact bundle, and termination. This manner of marked regeneration was also observed in the cerebellifugal projection, auditory pathway, vestibulospinal tract, and dorsal column axons. Thus, we conclude that whether or not axonal regeneration occurs depends on local condition of lesion rather than the global CNS axonal environment.<BR>Even in adult animals, embryonic brain tissue grafts introduced into the lesion site, which presumably contain axonal guidance cues by excising homotopic embryonal structure, induce marked and functionally active regeneration. The graft contains comprehensive axonal guidance cues, although the detailed mechanism of axonal guidance have yet to be elucidated sufficiently. The best treatment for brain and spinal cord injury is obviously to reconstruct the damaged neural connections. The enormous potential for regrowth and self-organization arouse a great hope for therapeutic breakthoughs in the near future.

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