Why does the central nervous system not regenerate after injury?

Abstract

A major problem for neuroscientists and clinicians is why the central nervous system shows ineffective regeneration after injury. Injured peripheral nerve fibers reform their connections, whereas those in injured spinal cord never re-grow. Insights into the mechanisms for repair and restoration of function after spinal cord injury have been obtained by experiments showing that injured nerve cells in the adult mammalian brain can indeed send out new fibers over a distance, if they are provided with appropriate tissue to grow along. Another major finding is that molecules exist in the CNS that inhibits the outgrowth of injured nerve cells. The aim of our experiments is to define more precisely changes that occur in devel¬opment, as the spinal cord changes from being able to regenerate to the adult state of failure. Our experiments show that after complete transection, spinal cords of newborn opossum pups regenerate provided that the animal is younger than about 12 days of age, after which the ability for repair becomes lost abruptly. We are now determining by subtractive suppression PCR which molecules decrease, and which inhibitory molecules increase during this critical period. Among growth-promoting genes we have found those for cadherin, catenin and molecules that affect transcription. Inhibitory genes include those associated with myelin and a different set of genes that affect transcription. Northern blots, reverse transcription PCR and in situ hybridization have confirmed these changes in gene expression. In spite of progress in many labs in recent years, major hurdles must be overcome before patients can be treated. Once a good understanding of mechanisms that promote and prevent regeneration is obtained, one will still have to de¬vise safe treatments for patients with spinal cord injuries, as well as methods for applying them. Nevertheless, the picture is not as bleak and dis¬couraging as it was: one can think today of strategies for doing research on spinal cord injury so as to promote regeneration and restore function.