The dorsal funiculus in cervical spinal cords of rats from 3 to 120 days postnatal was studied in order to document and quantitate d i a l cell development and axonal growth as related to the initiation and progress of central myelination. Within the dorsal funiculus are three major and distinct tracts, each having distinct developmental trends and adult characteristics in terms of fiber sizes and amount of myelin. These tracts are the cuneate and gracile fasciculi and the cortico-spinal tracts.Glial cell counts and cross-sectional surface area determinations of each tract at increasing ages show that the initial rate of d i a l population increase is similar. However, each tract is unique in terms of the age at which a maximum population density is reached and the rate at which the expected population dilution takes place. An electron-microscopic examination indicates that oligodendrocytes constitute over 85% of the total glial population throughout the development period surveyed. As such, these cells are primarily responsible for the population density changes.The diameters of unmyelinated fibers, promyelin fibers and some myelinated fibers in these tracts were measured at 5, 10, 15, 20 and 120 days postnatal. This was done both for the purpose of relating glial population density changes with the initiation and decline of active myelination, and for determining whether or not a critical diameter for myelination exists in the CNS as was found in peripheral nerves (Matthews, '68). For each tract there is a characteristic sequence of events involving not only myelination, but also changes in diameter distribution just prior to the appearance of myelin and during the period of active myelin formation. These events coincide with the concentration and dilution of the glial population, but it is also evident that there is no critical and constant diameter in the CNS above which all axons are myelinated and below which all are unmyelinated. Myelin appears first on larger axons, but as the animal matures, it is found on progressively smaller axons until between 20 and 120 days, axons 0.2-0.4 CL in diameter acquire myelin. Thus, myelination begins with axons destined to be large and then extends down to those which enlarge very little prior to acquiring myelin and remain very small even in adult animals.Finally, from the determination, in adult rats, of the number of axons and oligodendrocytes in a defined volume of each tract and an estimation of internode length, the ratio of internodes to oligodendrocytes was calculated. The specific values obtained could vary by as much as C 50% and are only meant to serve as indicators of a trend. However, it is suggested that the number of internodes per oligodendrocyte may be inversely proportional to the length of the internode.Characteristic changes jn the mitotic activity of glial cells prior to, during and after the initiation of myelin production have been studied by such workers as, Allen l T h i s T Z a r c h supported by NIII grants DHEW 5 T T z "~~"~~~~~~~~~~~~0...

Mid-thoracic dorsal and ventral roots from adult rats, cats and cows were prepared for electron microscopy using standard techniques. Axon diameters were measured on photographs of known magnification. Minimal diameters of the unmyelinated fibers in the spinal cords of these animals were measured also. With the exception of a few overlapping diameters unmyelinated fibers were smaller than the smallest myelinated fibers in all the material examined. In the dorsal roots of the cow, the unmyelinated fibers, as a group, were larger than those of the rat and cat, and very few were enclosed by any one Schwann cell. The largest unmyelinated fibers were singly enclosed. In addition, the dorsal root of the cow contains many more small myelinated fibers than those of the other two species. In the ventral roots, a progressive increase in the size and relative numbers of myelinated preganglionic fibers from rat through cat to cow was noted. These facts indicated that myelination is directly dependent on fiber diameter irrespective of age, species or function although less precisely than was indicated by the earlier studies of Duncan ('34). Although the critical diameter for myelination in the peripheral nervous system is about one micron, in the central nervous system it is 0.3 P or less.

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Transection of the spinal cord is adult Long-Evans Hooded rats is followed by the formation of a connective tissue matrix in the lesion site and the rapid erosion of the neural elements above and below this zone particularly within the dorsal white columns. In the period between 15--45 days after operation two significant events begin to occur. First the injured surfaces of the divided cord become invested by a glial limiting membrane (glia limitans) and, concomitantly, large numbers of axons ensheathed by Schwann cells sprout into the scar matrix and along the eroded dorsal column region. The injured surface of the spinal cord is highly irregular with deep, collagen-filled rifts into which the sprouting axons may probe and penetrate into the adjacent normal neuropil. Electron microscopic examination generally reveals the interposed glia limitans and that these fibres are usually restricted to the peripheral environment. However, as some axons approach the reconstituting glia limitans, they are enveloped by an astrocytic cytoplasmic process which may either displace the Schwann cell or encompass it together with the enclosed axons. This last phenomenon appears to precede the entry of some axons into the neuropil and suggests that the glia limitans may not necessarily represent an impenetrable barrier to the passage of regenerating axons into the CNS. Apparent maintenance of most of these fibres for periods of up to 3 months may suggest that viable, functional synapses were established upon available neuronal elements, but clear evidence of this could not be documented.

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Long-Evans hooded rats were cordotomized at the T-5 level and given either (1) cyclophosphamide (cytoxan), an immunosuppressive, (2) piromen, a bacterial polysaccharide-nucleic acid complex, (3) topical and systemic trypsin, or (4) no further specific treatment. Because of past and present controversy surrounding the proposed ability of these agents to promote spinal cord regeneration, a systematic study, employing light and electron microscopy, and quantitative methods in a single animal model, was done in order to re-evaluate the effects of each treatment upon the connective tissue matrix which forms in the defect left by transection. After an initial inflammatory reaction during the first week after surgery, the lesion zone is characterized either by areas of dense collagenous connective tissue with occasional fibroblasts and macrophages, or a loose areolar tissue with numerous sheets and cords of mesodermal cellular elements but minimal collagen. By 45 days postoperatively (dpo), axons supported by Schwann cells invade and become entangled in the loose connective tissue matrix. With longer postoperative survival, cysts appear craniad and caudad to the lesion and erode much of the scar together with viable neural tissue. Giving cytoxan or piromen did not result in any qualitative alteration of the scar matrix as evidenced by electron microscopy. Quantitative analysis revealed a slight reduction in the fibrous connective tissue component of the scar at 45--90 dpo, but this was transient when longer postoperative periods were studied. Trypsin caused a significant reduction in the amount of fibrous connective tissue with a concomitant increase in loose connective tissue and the appearance of a few distinctive, compact bundles of unmyelinated axons lacking Schwann cells. Consistent behavioral changes were not observed in any group which could distinguish them from the controls. Our results appear to contradict the findings of Matinian and Andreasian (1976) who reported return of normal sensori-motor function in 80% of their animals treated with topical and systemic trypsin. It is concluded that a major impediment to whatever longterm regenerative potential exists within the spinal cord is the lack of axonal guiding elements within the scar, but more importantly, the severe erosion of the remaining spinal cord due to cyst enlargement.