Onion-bulb formation after a single compression injury in the macrophage scavenger receptor knockout mice

Onion-bulb (OB) formation is often encountered in acquired neuropathies such as chronic inflammatory demyelinating polyradiculoneuropathy and diabetic neuropathy and is believed to require repeated injuries to peripheral nerves. Although this suggests that remaining damaged cell membranes, including myelin debris, might trigger OB formation, the molecular mechanism remains unclear. In this study, we were successful in producing many small OBs after a single compression injury to peripheral nerves of the knockout mice deficient of macrophage scavenger receptor class A (MSR-A). Although morphometry showed no difference in the average densities of the remaining myelinating fibers between wild-type and MSR-A knockout mice after the compression injury, there were more macrophages and myelin debris positive for oxidized-phosphatidylcholine in the nerves from the MSR-A knockout mice. We believe that OB formation was induced after a single compression injury as the result of delayed phagocytosis of myelin debris possessing oxidized lipids by MSR-A deficient macrophages. The present work shed light on the molecular mechanism of OB formation seen in chronic neuropathies and provided a model for further investigation.