In the central nervous system of adult mammals, including man, axonal regeneration following injury is much less successful than in the peripheral nervous system. However, previous experiments have shown that implanted segments of peripheral nerve will support growth of central axons. These results and others have suggested that the extraneural environment in peripheral nerve, including the extracellular matrix, can support growth of central axons. In these pilot studies we will test this hypothesis using components of the peripheral nervous system extracellular matrix that have been shown to promote and/or support neurite outgrowth in culture. These include collagen, fibronectin and laminin. The experimental paradigm will use the cat's dorsal lateral geniculate nucleus to assay for axonal growth. This nucleus contains cytologically distinct laminae that receive retinal input from one eye or the other; not both. Thus, retinal input to an inappropriate layer must represent abnormal axonal growth. Microliter syringes will be filled with matrix components, and the syringe needle will be lowered through the lateral geniculate nucleus, damaging cell bodies and axons. As the needle is withdrawn, matrix components will be injected along its track. Later, retinal projections to the nucleus will be mapped using H3-proline autoradiography or horseradish peroxidase histochemistry. Sections will then be examined for axonal growth along the syringe needle track, into an inappropriate geniculate layer. Preliminary studies using this procedure have produced positive results. In other experiments antibodies to matrix components will be used with immunocytochemical techniques to determine the spread and longevity of these components following injection into the brain. They will also reveal if these substances are produced endogenously in response to brain injury. The results should provide important new information about factors that affect axonal regeneration in the central nervous system.
