Anti-Nogo-A antibody treatment promotes recovery of manual dexterity after unilateral cervical lesion in adult primates--re-examination and extension of behavioral data.
In rodents and nonhuman primates subjected to spinal cord lesion, neutralizing the neurite growth inhibitor Nogo-A has been shown to promote regenerative axonal sprouting and functional recovery. The goal of the present report was to re-examine the data on the recovery of the primate manual dexterity using refined behavioral analyses and further statistical assessments, representing secondary outcome measures from the same manual dexterity test. Thirteen adult monkeys were studied; seven received an anti-Nogo-A antibody whereas a control antibody was infused into the other monkeys. Monkeys were trained to perform the modified Brinkman board task requiring opposition of index finger and thumb to grasp food pellets placed in vertically and horizontally oriented slots. Two parameters were quantified before and following spinal cord injury: (i) the standard 'score' as defined by the number of pellets retrieved within 30 s from the two types of slots; (ii) the newly introduced 'contact time' as defined by the duration of digit contact with the food pellet before successful retrieval. After lesion the hand was severely impaired in all monkeys; this was followed by progressive functional recovery. Remarkably, anti-Nogo-A antibody-treated monkeys recovered faster and significantly better than control antibody-treated monkeys, considering both the score for vertical and horizontal slots (Mann-Whitney test: P = 0.05 and 0.035, respectively) and the contact time (P = 0.008 and 0.005, respectively). Detailed analysis of the lesions excluded the possibility that this conclusion may have been caused by differences in lesion properties between the two groups of monkeys.
Freund
Patrick
P
Unit of Physiology and Program in Neurosciences, Department of Medicine, Faculty of Sciences, University of Fribourg, Chemin du Musée 5, CH-1700 Fribourg, Switzerland.
Schmidlin
Eric
E
Wannier
Thierry
T
Bloch
Jocelyne
J
Mir
Anis
A
Schwab
Martin E
ME
Rouiller
Eric M
EM
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002574:Cervical Vertebrae / Q000473:pathology; D005260:Female; D007839:Functional Laterality / Q000187:drug effects* / Q000502:physiology; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D009185:Myelin Proteins / Q000276:immunology*; D000070798:Nogo Proteins; D011597:Psychomotor Performance / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D018709:Statistics, Nonparametric; D013997:Time Factors
D000906:Antibodies; D009185:Myelin Proteins; D000070798:Nogo Proteins