The long-term objectives are to evaluate radiation-induced changes in the immature spinal cord, to use ionizing radiation as a tool to study reparative and regenerative capacities of the immature nervous system and to study normal development of the spinal cord.
The specific aims of the present project are to examine normal development and enhancement of regeneration in the spinal cord, taking advantage of two quite different but related radiation-induced situations. The first of these situations is a radiation-induced glial-deficient state which exists for a period of 2-3 weeks following irradiation of the 3-day-old rat. During this period, the population of glial cells (both astrocytes and oligodendrocytes) is markedly reduced. Since these cells are so intimately involved in neuronal development, maturation and function, this glial-deficient state is a model system in which to ask questions about growth patterns of developing axons, morphologic and electrophysiologic maturation of axons in the absence of their myelinating cells (oligodendrocytes), regeneration of axons in the absence of glial scarring (astrocytes), etc. The second rediation-induced situation or state begins during the 3rd post-irradiation week and involves the repair of the radiation-induced glial deficiency, at least in part, by development of Schwann cells in the spinal cord. Normally Schwann cells are restricted to the peripheral nervous system where they are the myelin-forming cells. Since Schwann cells are considered to play important role in regeneration in peripheral nerves, many other investigators have attempted to introduce these cells into the central nervous system (CNS) in an effort enhance its limited regenerative capacities. These attempts by others have met with only limited success, in contrast to the relatively extensive, predictable development of Schwann cells occurring in this radiation-induced situation. Therefore, because of this predictability in inducing Schwann cell development of the spinal cord, experiment are proposed to examine the possible role of Schwann cells in enhancing regeneration the CNS. Additionally, the proposed studies will deal with certain aspects of the signals for myelination and the interactions between the Schwann cells and the usual glial constituents. These studies will utilize both light and electron microscopy, immunocytochemistry, autoradiography, axonal tracing techniques and electrophysiology.
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