REGROWTH OF SPINAL CORD AXONS FOLLOWING COLD INJURY

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Utilizing a newly developed model which produces a freezing injury in rat spinal cords, the reparative and regenerative response of the tissue will be studied. The regrowth of axons in this experimental model provides opportunities to extend our understanding of the regenerative potential of mammalian central nervous tissue following traumatic or other injury. In these experiments we are specifically interested in three areas. In the first, we will develop more information about the current model, particularly in terms of the nature and source of the cellular matrix, the relationship of growing axons to the matrix, the breakdown of tissue in the Wallerian zone and the relationships of growing axons in the Wallerian zone. We will perform these studies, at first, upon the experimental form which is characterized by optimal development of the cellular matrix and axonal regrowth. This lesion will be identified in our initial experiments. Subsequently we plan to explore those lesions which represent identifiable variations from the optimal so as to examine more thoroughly the influence of axons, various glial elements, Schwann cells and mesenchymal components upon the regrowth of axons into the injury zone. Evaluation of these potential changes will be by electron microscopy and immunohistochemistry. Secondly, we will perform experiments which will verify the observation, made by light microscopy, that axons regrow into the lesion. These studies will be performed on the optimal model and on another model in which all the adjacent roots will be cut prior to freezing the cord. Analysis of the effects of these studies will be through the use of tracer techniques. Somatosensory evoked potentials will also be employed to permit in vivo evaluation of the status of axons within the lesion. Long range studies up to 18 months will determine whether axons can spontaneously regrow through the Wallerian zone following phagocytic clean-up of the area. And finally, we plan to investigate the following phagocytic clean-up of the area. We will study the vascular response to the lesion by measuring the permeability of intravenous horseradish peroxidase through the vessel walls. By light and electron microscopy the morphologic changes occurring in glia, axons, myelin, pial and subpial tissues will be evaluated. By immunohistochemistry we will attempt to identify other changes that may occur in the cellular and extra-cellular matrix.