How are sheath dimensions affected by axon caliber and internode length?

The significance of internode length for sheath thickness was analyzed by electron microscopic morphometry in isolated internodes from the human roots C3 and S1. These populations differ in length but have similar caliber. The amount of myelin per internode was in linear relation with the product of axon circumference and the length of the ensheathed axon segment. Neither one of these two vectors was in a statistically significant relationship with sheath thickness. The ratio between the axolemmal area covered by the Schwann cell and the area of the myelin leaflet averaged 1:163 for human root fibers. It was 1:177 for previous data from canine sciatic nerve. The proportions of an internode were defined by an 1/d-quotient, expressing its length as multiples of axon diameter. Relative sheath thickness (g-ratio: diameter axon/diameter fiber) relates inversely with the 1/d-quotient. For a given axon caliber, the g-ratio (sheath thickness) decreases by 0.006 for every 10.0 increase in 1/d-quotient (relative internode length). Thus, internodes relatively long for axon caliber possess slightly thicker sheaths than internodes short for axon caliber. Axon caliber and relative internode length emerge as the two key factors determining the amount of myelin in a sheath.

The organization of endoneural collegen in peripheral nerves as revealed with the scanning electron microscope.

Transmission electron microscopy of isolated nerve fibers of rat sciatic nerve and scanning microscopy of small groups of fibers reveal that the majority of collagen fibrils form tightly woven cuffs around individual nerve fibers. Only a small fraction of the fibrils is not associated with individual nerve fibers and forms a loose, wide-meshed net between them. These observations reconfirm the pre-electron-microscopic concept of a sheath of Key and Retzius or of Plenk and Laidlaw, respectively.

The precise geometry of large internodes.

The interrelations, in each given internode, between internodal length, axon caliber, axoplasmic volume and several parameters of sheath thickness were studied in a set of 37 large internodes from the sciatic nerve of the German shepherd dog, using multiple electron-microscopic measurements of isolated fibers. Internodal length varied in a nonlinear relation with axon caliber. Nonlinear relations were also found for the number of lamellae in the sheath as related to either axon caliber or to internodal length, particularly for large internodes: the deviations observed for axon caliber (thick fibers had fewer myelin lamellae than would correspond to axon caliber) were the opposite of for internodal length (thick fibers had more lamellae than would correspond to internodal length). A near linear relationship was found if the volume of myelin per internode was related to both the length and the circumference of the axon segment ensheated by it, i.e., axolemmal surface area. The deviations in the proportions of large internodes probably indicate the existence of upper limits of internodal growth conditioned by the enormous metabolic demands placed on the individual Schwann cell by the growth of internodes beyond 1.5--2 mm length or 100 thousand micrometer3 of myelin, respectively. The demands on myelin metabolism from unabated internodal growth and the resultant logistic problems of the Schwann cells are demonstrated from measurement of observed internodes and calculations of extrapolated growth.

The fine structure of stumps of transected nerve fibers in subserial sections.

The proximal stumps of five rat sciatic fibers, transected 72 hr earlier, were reconstructed on the basis of morphometry in subserial electron micrographs of isolated fibers. Three fibers showed extensive axon sprouting; 2 had no sprouts but were excessively swollen. The total volume of axoplasm in the axon swellings approximated the volume of axoplasm in all sprouts of any given fiber. Axonal swelling therefore may ensur when sprouting is frustrated. Axon sprouts originated mostly at nodes from where they descended or ascended along the fiber, running within its lamina basalis. Sprouting began soon after injury, usually within the first day. Counts of microtubules showed an approximately 10-fold increase in the total number of tubules per fiber toward the injured end. Schwann cells showed asymmetric hypertrophy, having distinctly more cytoplasm distally than proximally to the nucleus. The increase in Schwannian cytoplasm occurred roughly pari-passu with the increases in axoplasm. Hypertrophy of Schwann cells was associated with cytoplasmic islands or strands having an extremely variable content of organelles. Such islands of Schwannian cytoplasm may be confused with axon sprouts. Retraction of the myelin sheaths at nodes results in fiber profiles suggestive of partial demyelination. Retraction of nodal pseudopodia produces redundant loops of lamina basalis. Migratory cells are seen outside the fibers or underneath their lamina basalis having a preference for nodal regions or for the fiber stump. They behave differently toward axon or myelin: they encompass axon sprouts as do immature Schwann cells; simultaneously the same cell may invade myelin sheaths like a macrophage. Other curious overlaps of degenerative and regenerative phenomena were noted, including an axon sprout tunneling through the lumen of the sequester of the myelin sheath of its parent axon.

How do axons control myelin formation? The model of 6-aminonicotinamide neuropathy.

Injection of 6-aminonicotinamide into young rats produces a peculiar neuropathy characterized by selective swelling and disruption of the layer of Schwann cell cytoplasm lining the inner surface of the myelin sheath. This layer increases greatly in volume, compressing the axon and distending the myelin sheath. Morphometry of such swollen fibers discloses that the amount of myelin in the distended sheaths is considerably greater than would correspond to the size of the axons, even if axonal compression is accounted for. The data favor the concept that sheath growth is stimulated by non-specific distension of the myelin sheath from inside.

Production of myelin by neoplastic cells.

Formation of myelin sheaths by neoplastic cells was found in a spinal ganglioneuroma. All phases of initial myelination were observed including the formation of a mesaxonal spiral and the fusion of its lamellae into a major dense line. A unique aspect of neoplastic myelin formation was the formation of sheaths around bundles of extracellular fibrils rather than axons or cell processes. Formation of myelin sheaths around extracellular material has never been observed before. The findings have implications on the mechanisms controlling initial myelination.