Axons that have been disconnected form the injury site must grow all the way back to their original cells to reconnect with them. Axons that have been damaged will sprout short distances but they often stop at the injury site. There is much debate concerning why the axons do not continue growing. Several theories have been popular. For many years, scientists thought that glial cell proliferation (glial scar) around the injury site mechanically prevented axonal growth.
However, this mechanical obstruction theory lost favor as many scientists have shown that axons can grow through glial scars under certain circumstances. So many scientists now think that glial cells release a chemicals that stop axonal growth. In particular, glia and inflammatory cells secrete chondroitin 6-sulfate proteoglycan (CSPG), a chemical that strongly inhibits axonal growth.
Other scientists believe that oligodendroglial cells express proteins that stop growth. Many studies have shown that axons don’t like to grow on tissues that contain myelin produced by oligodendroglia. The leading candidate myelin-associated molecule that has been shown to stop axonal growth is a protein called Nogo. Oligodendroglial myelin has Nogo on the surface. The antibody called IN-1 blocks Nogo and has been shown to regenerate the spinal cord. Martin Schwab developed this antibody and is likely to go into clinical trial. Other scientists have identified a molecule called myelin-associated glycoprotein or MAG that stops axonal growth.
Still other scientists believe that axonal growth is stopped by an extracellular matrix protein called collapsin; this protein has been identified to be part of a family of proteins called semaphorin and is now called Sema III. But I want to remind you of two obstacles to effective regeneration that we do not usually consider: time and distance. Axons grow slowly, probably no faster than our hair grows, at about a mm a day at fastest. Thus, it takes months or years for an axon to grow the entire distance from the injury site back to the neurons that they use to innervate. The axon may simply stop growing after a while. If the axon does not reach a target by a certain time, it stops growing and may die back.
