Regeneration of brainstem-spinal axons after lesion and immunological disruption of myelin in adult rat

We previously observed that the transient developmental suppression of myel ination or disruption of mature myelin, by local intraspinal infusion of se rum complement proteins along with a complement-fixing, myelin-specific ant ibody (e.g., anti-Galactocerebroside), facilitated avian brainstem-spinal a xonal regeneration after spinal transection. We now report the effects of s imilar immunological protocols on axonal regeneration in the injured adult rat spinal cord. After a lateral hemisection injury of the T10 spinal cord, infusion of the above reagents, over 14 days at T11, facilitated the regen eration of some brainstem-spinal axons, The hemisection lesion enabled comp arisons between the retrograde labeling within an injured brainstem-spinal nucleus and the uninjured contralateral homologue. The brainstem-spinal nuc leus examined in detail was the red nucleus (RN), chosen for its relatively compact descending pathway within the dorsolateral cord. Comparing the num ber of labeled neurons within each RN, of an experimentally myelin suppress ed animal, indicated that approximately 32% of injured rubrospinal projecti ons had regenerated into the caudal lumbar cord. In contrast, control-treat ed animals (e.g., PBS vehicle alone, GalC antibody alone, or serum compleme nt alone) showed little or no axonal regeneration. We also examined the ult rastructural appearance of the treated cords. We noted demyelination over 1 -2 segments surrounding the infusion site (T11) and a further two segments of myelin disruption (delamination) on either side of the demyelinated zone . The demyelination is an active process (<3 days) with microglia and/or ma crophages engulfing myelin. Thus, the facilitation of axonal regeneration t hrough the transient suppression of CNS myelin may be fundamental to all hi gher vertebrates. (C) 1998 Academic Press.