Morphometric alteration of rat myelinated fibers with aging.

The number, size, density and pathologic alterations of myelinated fibers (MF) of ventral and dorsal roots and of peroneal and sural nerves in groups of female Fischer 344 rats at 10, 20, and 30 months of age were evaluated to characterize nerve changes with old age. Except for minimal changes in the peroneal nerve, no statistically significant alteration in number of MF/nerve or in the fascicular area was associated with aging. The unaltered number was misleading since striking changes in MF size distribution, pathologic alterations of fibers and the presence of regeneration clusters suggested age-related degenerative and regenerative events. These changes were most dramatic in the ventral root, where myelin infolding, myelin separation from axon and ballooning, macrophagia and hyperplasia of Schwann cell nuclei were pronounced. Concomitant with these alterations, axonal atrophy (a reduction in caliber of axons relative to myelin spiral length or number of myelin lamellae) was demonstrated in MF of the ventral root in old age.

Alpha-melanocyte-stimulating hormone stimulates the outgrowth of myelinated nerve fibers after peripheral nerve crush.

The effect of alpha-melanocyte-stimulating hormone on peripheral nerve regeneration was studied by monitoring functional recovery and quantifying histologic changes that follow crush lesion of the rat sciatic nerve. The results showed that such treatment of rats with a crushed sciatic nerve resulted in a reduction of the recovery period and in an increase in the number of regenerating nerve fibers.

Postnatal loss of axons in normal rat sciatic nerve.

Myelinated and unmyelinated axons were counted in sciatic nerves of newborn, 5-day-old, 14-day-old, and adult rats. Myelinated axons increase from essentially none at birth to approximately 8,000 in adulthood, but total axon numbers decrease steadily from 33,954 at birth to 22,872 in adulthood. Thus there is a significant postnatal loss of axons from rat sciatic nerve. This loss is, in our opinion, not associated with the death of the cells that give rise to these axons. This is thus an example of a regressive event that probably is of importance in normal neural development, namely the postnatal elimination of axons unaccompanied by death of the neurons that give rise to axons. These findings presumably imply a considerable amount of proximal peripheral axon branching, and the postnatal elimination of axons in the sciatic nerve presumably results from a reduction of this branching. Thus postnatal elimination of processes on, for example, somatic muscle cells may be at least partially the result of long axon elimination rather than local withdrawal of presynaptic processes, as is usually thought to be the case. In addition, an increased number of axons resulting from early postnatal manipulations may indicate cessation of axon loss rather than formation of new axons.

Membrane ultrastructure of developing axons in glial cell deficient rat spinal cord.

In order to investigate axolemmal development in a glial cell deficient environment, normal and irradiated dorsal funiculus in rat lumbosacral spinal cord was examined by freeze-fracture electron microscopy. At 3 days of age, normal fibres are all unmyelinated and of small (less than 0.5 micron) diameter. The unmyelinated axons have a moderate density (approximately 850 microns-2) of intramembranous particles (IMPs) on P-fracture faces and a low IMP density (approximately 300 microns-2) on E-faces. IMPs are homogeneously distributed along both fracture faces. By 19 days of age, the normal dorsal funiculus is well populated with myelinated axons and glial cells, as well as a sizable population of unmyelinated fibres. Nearly all of the myelinated fibres have a large (greater than 1.0 micron) diameter; whereas, most unmyelinated axons are of small (less than 0.5 micron) calibre. The axolemma of unmyelinated axons is relatively undifferentiated, with an asymmetrical distribution of IMPs (P-face: approximately 1100 microns-2; E-face: approximately 450 microns-2). Myelinated fibres show nodal and paranodal regions with P-face and E-face ultrastructure similar to previous descriptions. Internodal axolemma appears relatively homogeneous, with P-faces being highly particulate (approximately 2100 microns-2) and a low IMP density (approximately 200 microns-2) on E-faces. Following irradiation of the lumbosacral spinal cord at 3 days of age, there is a severe reduction in the number of glial cells and myelinated fibres in this region when the tissue is examined at 19 days of age. Despite the deficiency of glial cells in this tissue, axonal and axolemmal development continue. Numerous large (greater than 1.0 micron) diameter axons are present in this irradiated tissue. Large diameter axons show a high (approximately 2000 microns-2) density of IMPs on P-faces; E-face IMP density remains at approximately 440 micron-2. Small calibre axons also have an asymmetrical distribution of particles (P-face: approximately 1100 microns-2; E-face: 280 microns-2). The axolemmal E-faces of some glial cell deprived fibres exhibit regions with greater than normal (approximately 750 microns-2) density of IMPs. These results demonstrate that some aspects of axonal and axolemmal development continue in a glial cell deficient environment, and it is suggested that axolemmal ultrastructure is, at least in part, independent of glial cell association.

Axolemmal differentiation in myelinated fibers of rat peripheral nerves.

In developing rat peripheral fibers, nodal specialization appears early, prior to myelin compaction, and is first detected as a junction between the axon and the overhanging Schwann cell process characterized by a uniformly wide (approximately 18 nm) intercellular gap containing a patchy dense substance and a cytoplasmic undercoating subjacent to the axolemma. The gap width is rather consistent but the axolemmal undercoating is more variable and lower in density than that found at more mature nodes of Ranvier, and it is also highly variable in length, ranging from 0.5 to 3 micron. The outermost Schwann cell layer is usually prominent with a large volume of cytoplasm and many organelles. In freeze-fracture replicas, modal specializations are characterized by accumulations of large (approximately 10 nm) particles in the axolemma, especially the E face, but immature nodes generally have a lower particle concentration than mature nodes. No node-like particle aggregates have been found in axons not intimately associated with Schwann cells. Mature paranodal axon-Schwann cell junctions are usually formed first by the loops closest to the node and are characterized by a 2-3 nm gap between the apposed membranes, periodic intercellular densities (transverse bands) in the gap and cisternae flattened against the junctional Schwann cell membrane. The loops further removed from the node display a wider gap containing irregularly spaced or diffuse intercellular densities, or none. Mature junctions appear relatively late in the rat, and it is not unusual to find developing nodes with several Schwann cell loops present that do not indent the axolemma significantly and are not associated with the paracrystalline pattern characteristic of the mature junctional axolemma. In such instances, the nodal particle aggregates do not have sharply circumscribed boundaries. The majority of the developing nodes are asymmetric with one paranodal segment more mature than the other.

The myelination of the cerebellar cortex in the cat.

The myelination of the cerebellar cortex of the cat was investigated in 61 cats aged from 3 hrs post partum to two and a half years. The first myelinated fibers appear at the time of birth in the central medullary ray. Before the onset of myelination, all fibers reach a critical diameter of about 1 micrometer. About the 14th day of life the number of oligodendrocytes in the prospective while matter increases markedly. Thereafter, the oligodendrocytes invade the inner granular layer. It therefore seems that the myelination of the cerebellar cortex proceeds from the central medullary ray towards the granular layer. At the 60th day of postnatal life, most of the afferent and efferent fiber systems are myelinated. These findings are discussed in relation to the development of function and the maturation of the electrical activity of the cerebellar circuit.

[Mathematical analysis of myelin structure of nerves of the brachial plexus in antenatal and early postnatal ontogenesis of man]. / Matematicheskii analiz mieloarkhitektoniki nervov plechevogo spleteniia v antenatal'nom i rannem postnatal'nom ontogeneze cheloveka

A gradual increase of the information entropy indices and a decrease of the excess percentage is observed in the course of antenatal and early postnatal ontogenesis of man. The indices of the information entropy reach their maximum and the excess percentage reaches its minimum in children younger than 3 years. At that time the myelinated fibres have the most various diameters. In the antenatal development of man the prevalence of fine (1--4 mkm) myelinated fibres makes the structure of the humeral plexus nerves more definite while in the postnatal ontogenesis their structure is less definite since the myelinated fibres of different diameter are met with almost the same probability.

The rodent incisor tooth proliferon.

The rodent incisor tooth is the site of five cell populations proliferating in harmony: amelocytes, odontocytes, pulp cells, endothelial cells and the periodontal ligament. Their proliferating regions are located in the apex tip, where the various cells originate. Cells displaced from the tooth origin at the apex toward the periphery, mature to perform their specified function. The proliferative events in the tooth are summarized in a conceptual model of the incisor proliferon. The proliferon is an oriented structure with an origin and periphery. It consists of four basic elements: parenchyma, connective tissue, blood vessels and nerve fibres, all interacting continuously. All four are indispensable in the definition of the proliferon.