Regeneration of brainstem-spinal axons after lesion and immunological disruption of myelin in adult rat.
We previously observed that the transient developmental suppression of myelination or disruption of mature myelin, by local intraspinal infusion of serum complement proteins along with a complement-fixing, myelin-specific antibody (e.g., anti-Galactocerebroside), facilitated avian brainstem-spinal axonal regeneration after spinal transection. We now report the effects of similar 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 regeneration of some brainstem-spinal axons. The hemisection lesion enabled comparisons between the retrograde labeling within an injured brainstem-spinal nucleus and the uninjured contralateral homologue. The brainstem-spinal nucleus examined in detail was the red nucleus (RN), chosen for its relatively compact descending pathway within the dorsolateral cord. Comparing the number of labeled neurons within each RN, of an experimentally myelin suppressed animal, indicated that approximately 32% of injured rubrospinal projections had regenerated into the caudal lumbar cord. In contrast, control-treated animals (e.g., PBS vehicle alone, GalC antibody alone, or serum complement alone) showed little or no axonal regeneration. We also examined the ultrastructural 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 macrophages engulfing myelin. Thus, the facilitation of axonal regeneration through the transient suppression of CNS myelin may be fundamental to all higher vertebrates.
Dyer
J K
JK
Department of Zoology, University of British Columbia, Vancouver, Canada.
Bourque
J A
JA
Steeves
J D
JD
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019771:Axotomy; D001933:Brain Stem / Q000737:chemistry / Q000502:physiology*; D003165:Complement System Proteins / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000276:immunology; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis; D005699:Galactosylceramides / Q000276:immunology; D006651:Histocytochemistry / Q000379:methods; D009186:Myelin Sheath / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D009416:Nerve Regeneration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012012:Red Nucleus / Q000737:chemistry / Q000502:physiology; D013116:Spinal Cord / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D013266:Stilbamidines
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D000906:Antibodies; D005456:Fluorescent Dyes; D005699:Galactosylceramides; D013266:Stilbamidines; C002454:galactocerebroside; D003165:Complement System Proteins