A Biochemical and Morphologic Study of Myelination and Demyelination

Bilateral transection was performed on rat sciatics. At varying intervals after the operation, samples of nerve were taken both distal and proximal to the level of transection, as well as from the tissue which bridged the gap between the stumps. These samples were incubated in Warburg flasks, with glucose and a labelled lipide precursor (acetate or phosphate). The total lipides were then extracted and their radioactivity was measured. Normal rat sciatics served as controls, and the biochemical and histological findings were correlated. In the distal portion undergoing Wallerian degeneration, the lipide content began to fall before any removal of myelin could be detected histologically. It is suggested that there is a period of "non-cellular removal" prior to the physical breakdown of the myelin. Changes in respiration and in lipogenesis from acetate followed a triphasic course, and agreed with the histological findings in that after a period of predominantly passive changes (approximately 1 to 3 days) there follows a period of cellular reaction (4 to 50 days) and a period of atrophy (from 50 days onward). The incorporation of phosphate into the lipides was increased at all stages examined, even as early as 22 hours after section. This increased P(32) incorporation could not be reproduced in nerves allowed to degenerate in vitro. It is suggested that the hypertrophying Schwann cells synthesize some lipide moieties at a considerably faster rate than others. Proximal to the level of transection, lipogenesis from acetate was depressed, for as long as 32 days postoperatively. It appears, therefore, that the maintenance of the myelin sheath is impaired also above the level of transection. In the "union tissue" which developed between the stumps, prior to the appearance of histologically visible myelin, lipogenesis was low; later it rose above levels for normal nerve. This pattern of lipogenesis in regenerating nerve is similar to that found in growing nerves.