Antibodies to myelin-associated glycoprotein accelerate preferential motor reinnervation.
Predegeneration of nerve enhances its ability to support axon regeneration. Trophic factors are upregulated by reactive Schwann cells while potentially inhibitory molecules are removed. These experiments isolate the effects of one such inhibitory molecule, the myelin-associated glycoprotein (MAG), to determine its role in modifying regeneration after nerve repair. Suture of the mouse femoral nerve was followed by daily intraperitoneal injection of antibodies to MAG, antibodies to HNK-1, a specific muscle pathway marker, or no further treatment. Regeneration was assayed by double-labeling the femoral cutaneous and muscle branches with horseradish peroxidase and fluoro-gold after 4 weeks or 6 weeks of regeneration. Four weeks after nerve repair, selective reinnervation of the muscle branch by motoneurons, or preferential motor reinnervation (PMR), was not seen in either controls or L2-antibody-treated animals. In contrast, treatment with MAG antibodies resulted in dramatic PMR. By 6 weeks, the controls had achieved borderline specificity, substantial PMR developed in the L2 antibody group and the MAG group changed little. Blocking access to MAG in the distal nerve stump thus accelerated and enhanced PMR. Sensory regeneration was depressed by both antibody treatments at 4 weeks but recovered by 6 weeks. Antibody administration has a generalized effect on sensory regeneration that is unrelated to the behavior of motoneurons in the same nerve.
Mears
Simon
S
Department of Orthopaedic Surgery, Johns Hopkins Medical Institutions, 601 North Caroline Street, Baltimore, MD 21287, USA.
Schachner
Melitta
M
Brushart
Thomas M
TM
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000502:physiology; D018959:CD57 Antigens / Q000276:immunology / Q000502:physiology; D005267:Femoral Nerve / Q000187:drug effects*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009132:Muscles / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000276:immunology* / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D012867:Skin / Q000294:innervation / Q000378:metabolism; D013266:Stilbamidines; D013997:Time Factors
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D000906:Antibodies; D018959:CD57 Antigens; D005456:Fluorescent Dyes; D018992:Myelin-Associated Glycoprotein; D013266:Stilbamidines; D006735:Horseradish Peroxidase