An explanation of axonal regeneration in peripheral nerves and its failure in the central nervous system

Abstract

Nerve fibres severed within peripheral nerves are able to regenerate and reinnervate the structures they formerly supplied. Most axons severed within the mammalian central nervous system (CNS) do not regenerate in this way. Regenerative axonal growth begins to occur in the CNS but ceases about two weeks after injury. Five earlier theories purporting to explain this difference are reviewed and found not to account satisfactorily for many experimental observations. A new hypothesis is advanced in which it is held that in order for regeneration to take place, the growing tips of the axons must be surrounded by extracellular fluid containing proteins (of specified identity) derived from the blood plasma. Such proteins are thought to be imbibed by the tips of the fibres and transported retrogradely to the neuronal cell-bodies. With this hypothesis it is possible to explain the success of axonal regeneration in peripheral nerves and its failure in the CNS. It is also possible to account for the exceptional circumstances in which axons do regenerate in the CNS. Various experiments are suggested for testing the validity of the new hypothesis.