Anti-Nogo-A antibody treatment enhances sprouting of corticospinal axons rostral to a unilateral cervical spinal cord lesion in adult macaque monkey.
After injury, regrowth of axons in mammalian adult central nervous system is highly limited. However, in monkeys subjected to unilateral cervical lesion (C7-C8 level), neutralization of an important neurite outgrowth inhibitor, Nogo-A, stimulated axonal sprouting caudal to the lesion, accompanied by enhanced functional recovery of manual dexterity, compared with lesioned monkeys treated with a control antibody (Freund et al. [2006] Nat. Med. 12:790-792). The present study aimed at comparing the same two groups of monkeys for axonal sprouting rostral to the cervical lesion. The corticospinal tract was labeled by injecting the anterograde tracer biotinylated dextran amine into the contralesional motor cortex. The corticospinal axons were interrupted at the level of the lesion, accompanied by retrograde axonal degeneration (axon dieback), reflected by the presence of terminal retraction bulbs. The number of terminal retraction bulbs was lower in anti-Nogo-A antibody treated monkeys, and, when present, they were found closer to the lesion than in control-antibody treated monkeys. Compared with control antibody treated monkeys, the anti-Nogo-A antibody treated monkeys exhibited an increased cumulated axon arbor length and a higher number of axon arbors going in the medial direction from the white to the gray matter. Higher in the cervical cord (at C5 level), the anti-Nogo-A treatment enhanced the number of corticospinal fibers crossing the midline, suggesting axonal sprouting. Thus, the anti-Nogo-A antibody treatment enhanced axonal sprouting rostral to the cervical lesion; some of these fibers grew around the lesion and into the caudal spinal segments. These processes paralleled the observed improved functional recovery.
Freund
Patrick
P
Unit of Physiology and Program in Neurosciences, Department of Medicine, Faculty of Sciences, University of Fribourg, CH-1700 Fribourg, Switzerland.
Wannier
Thierry
T
Schmidlin
Eric
E
Bloch
Jocelyne
J
Mir
Anis
A
Schwab
Martin E
ME
Rouiller
Eric M
EM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D001710:Biotin / Q000031:analogs & derivatives; D002452:Cell Count; D048429:Cell Size / Q000187:drug effects; D003911:Dextrans; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D020439:Growth Cones / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D009185:Myelin Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000276:immunology; D000070798:Nogo Proteins; D011712:Pyramidal Tracts / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016896:Treatment Outcome
D000906:Antibodies; D003911:Dextrans; D009185:Myelin Proteins; D000070798:Nogo Proteins; C076397:biotinylated dextran amine; D001710:Biotin