The cerebral white matter of rats subjected to a variety of noxious experimental conditions was examined in the electron microscope. Several unusual configurations of the myelin sheath are identified in addition to the usual configuration. These variations include the presence of (a) formed organelles within the inner and outer loops, (b) isolated islands of cytoplasm in unfused portions of the major dense lines, (c) apparently unconnected cell processes between the sheath and the axon, and (d) concentric, double myelin sheaths. A generalized model of the myelin sheath based on a hypothetical unrolling of the sheath is described. It consists of a shovel-shaped myelin sheet surrounded by a continuous thickened rim of cytoplasm. Most of the unusual myelin configurations are explained as simple variations on this basic theme. With the help of this model, an explanation of the formation of the myelin sheath is offered. This explanation involves the concept that myelin formation can occur at all cytoplasmic areas adjacent to the myelin proper and that adjacent myelin lamellae can move in relation to each other.By now, the theory of spiral wrapping by a single cell process is generally accepted as the main method by which myelin is formed in the vertebrate central nervous system, both in myelinogenesis and in remyelination (5-7, 11, 18, 25, 26, 28, 29-31, 34, 36, 37). The great majority of published micrographs and, indeed, those seen in our own laboratory may be interpreted on this basis. Occasionally, however, profiles of the myelin sheath are observed which, while they do not speak against the spiral-wrapping theory, require a more complex explanation than the simple uniform wrapping of a myelin-forming cell process around an axon.These profiles, relatively rare under normal conditions, are quite frequent under pathological or experimental conditions. Such profiles include those showing isolated cytoplasmic islands within incompletely fused major dense lines (6,11,26), unconnected cell processes between the innermost myelin lamallae and the axons (6,19,29,34), and double, concentric sheaths surrounding a single axon (I 1, 13).It is the purpose of the present paper to describe these configurations under a variety of experimental conditions and to present a uniform, generalized model of the myelin sheath in the central nervous system basically similar to that presented by Robertson (33) for the peripheral nervous system. This model not only will, we feel, serve to explain the anatomy of most of the above mentioned configurations but, also will be useful in explaining some of the processes involved in myelinogenesis and remyelination.
MATERIALS AND METHODSSeveral experimental procedures were used in the present study, all of which yielded essentially similar results. The procedures included cyanide intoxication (9, 22), experimental allergic encephalomyelitis (17), dibenzanthracene implantation (3, 12), cold injury (14, 20, 35), and Cryptocovcus neoformans (21) as well as purified cryptococcal polysaccharide...