Luckily, adult neurons remain able to respond to axon-regenerating signals from such factors. Obviously, however, natural production of these substances falls far short of the amount needed for spinal cord repair. Indeed, manufacture of some of the compounds apparently declines, instead of rising, for weeks after a spinal trauma occurs. According to a host of animal studies, artificially raising those levels after an injury can enhance regeneration. Some regeneration- promoting neurotrophic factors, such as basic fibroblast growth factor, have been tested in stroke patients. None has been evaluated as an aid to regeneration in people with spinal cord damage, but many are being assessed in animals as a prelude to such studies.
Those considering neurotrophic factors for therapy will have to be sure that the agents do not increase pain, a common long-term complication of spinal cord injury. This pain has many causes, but one is the sprouting of nascent axons where they do not belong (perhaps in a failed attempt to address the injury) and their inappropriate connection to other cells. The brain sometimes misinterprets impulses traveling through those axons as pain signals. Neurotrophic factors can theoretically exacerbate that problem and can also cause pain circuits in the spiral cord and pain-sensing cells in the skin to become oversensitive.
After axons start growing, they will have to be guided to their proper targets, the cells to which they were originally wired. But how? In this case, too, studies of embryonic development have offered clues.
During development, growing axons are led to their eventual targets by molecules that act on the leading tip, or growth cone. In the past five years especially, a startling number of substances that participate in this process have been uncovered. Some, such as a group called netrins, are released or displayed by neurons or glial cells. They beckon axons to grow in some directions and repel growth in others. Additional guidance molecules are fixed components of the extracellular matrix. Certain of the matrix molecules bind well to specific molecules (cell adhesion molecules) on the growth cones and thus provide anchors for growing axons. During development, the required directional molecules are presented to the growth cones in specific sequences.
Establish Proper Connections
At the moment, no one knows how to supply all the needed chemical road signs in the right places. But some findings suggest that regeneration may be aided by supplying just a subset of those targeting molecules—say, a selection of netrins and components from the extracellular matrix. Substances already in the spinal cord may well be capable of supplying the rest of the needed guidance.
A different targeting approach aims to bridge the gap created by cord damage. It directs injured axons toward their proper destinations by supplying a conduit through which they can travel or by providing another friendly scaffolding able to give physical support to the fibers as they try to traverse the normally impenetrable cyst. The scaffolding can also serve as a source of growth-promoting chemicals.
For instance, researchers have implanted tubes packed with Schwann cells into the gap where part of the spinal cord was removed in rodents. Schwann cells, which are glia of the peripheral nervous system, were chosen because they have many attributes that favor axonal regeneration. In animal experiments, such grafts spurred some axonal growth into the tubes.
A second bridging material consists of olfactory-ensheathing glial cells, which are found only in the tracts leading from the nose to the olfactory bulbs of the brain. When those cells were put into the rat spinal cord where descending tracts had been cut, the implants spurred partial regrowth of the axons over the implant. Transplanting the olfactory-ensheathing glia with Schwann cells led to still more extensive growth.